This site offers answers on special questions. The answers may not always be up-to-date.
- 1 This site offers answers on special questions. The answers may not always be up-to-date.
- 2 Cannabis Strains: Do Cannabis Strains Differ?
- 3 Cannabis oil: What is the best and healthiest way to produce cannabis oil?
- 4 Cancer: Do cannabinoids cure cancer?
- 5 Schizophrenia: Does cannabis use increase the risk for schizophrenia?
- 6 Anxiety: Does cannabis cause anxiety or does it reduce anxiety or may both occur?
- 7 Rare vegetative side effects: Can increased blood pressure, headache, chills, nausea, and belly ache be ascribed to cannabis use?
- 8 Gastric ulcer: Can cannabis be helpful in gastric ulcers?
- 9 THC in blood: How long can THC and his metabolites be detected in blood?
- 10 Children: What is known about the medical use of cannabis in children?
- 11 Detection of cannabis consumption: Can the use of cannabis be detected in blood or urine with routinely laboratory tests?
- 12 Dosing with oral use: What doses are used if THC (dronabinol) or cannabis is ingested, in capsules, in cookies or as cannabis tea?
- 13 Cognitive performance: Does long-term use of cannabis impair intellectual ability?
- 14 Heating of cannabis: Why should cannabis products be heated before eating?
- 15 Risks of smoking: What are the major strategies to reduce the risks of cannabis smoking?
- 16 Urine tests: How long can THC metabolites be detected in urine?
- 17 Cannabis tincture: How can I prepare a cannabis tincture or cannabis oil?
- 18 Heart attack: Does cannabis use cause heart attacks?
- 19 Chromosomal damage: Does cannabis cause damage to the genes?
- 20 Male fertility: Do cannabis or THC have a negative influence on sex hormones and sperms?
- 21 Asthma: How should cannabis or THC be taken to treat asthma?
- 22 Interaction: Does cannabis/THC interact with other drugs used for the treatment of diseases?
- 23 Pregnancy: Does cannabis/THC do harm to the fetus if it is used during pregnancy?
Cannabis Strains: Do Cannabis Strains Differ?
By Dr. Ethan Russo
Cannabis consumers have always maintained that different types (strains, or chemical varieties, chemovars) produce distinct effects, whether this be with respect to their psychoactivity or to their therapeutic attributes. Strains are often designated as sativa, indica, or a hybrid. These labels are quite misleading as applied in the marketplace, however. In contrast, the scientific community has generally focused on tetrahydrocannabinol (THC) as the primary or only important variable. It is clear that until very recently, selective breeding in cannabis for the recreational and medicinal markets have produced THC-predominant cannabis to the exclusion of other cannabinoids. Some researchers have stressed the importance of additional components, especially terpenoids, the aromatic components of cannabis that like cannabinoids are produced in glandular trichomes, as important modulators of cannabis effects (McPartland & Russo, 2001, Russo 2011).
What are other cannabinoids in cannabis?
The most common phytocannabinoid besides THC is cannabidiol (CBD). It was previously common in cannabis landraces from Afghanistan and Morocco, for example, but has largely disappeared from recreational cannabis. It is also present in hemp fibre and seed strains, but usually in low titre. In the medicinal arena, CBD has received increasing attention due to its many medicinal attributes, including its pain-relieving and anti-inflammatory benefits without intoxication or sedation. It also reduces side effects of THC when administered concomitantly, specifically, anxiety and tachycardia. Taken together, the two components may demonstrate synergy in many applications.
Another cannabis component of interest is tetrahydrocannabivarin (THCV), traditionally found in small amounts in Southern African cannabis chemovars (chemical varieties). It is currently under investigation as a treatment for metabolic syndrome, often seen as a prelude to the development of Type II diabetes.
Other phytocannabinoids under investigation include cannabigerol (CBG) for prostate cancer, cannabidivarin (CBDV) for epilepsy, and several others.
What about terpenoids?
Abundant evidence supports that these low concentration components contribute to the phytocannabinoids in whole cannabis preparations by adding their own therapeutic benefits or allaying side effects of THC. Worthy of particular mention are limonene, with known anti-depressant effects, pinene, which attenuates short-term memory deficits engendered by THC, myrcene, which is sedating, and beta-caryophyllene, which stimulates the non-psychoactive CB2 receptor, and produces anti-inflammatory and analgesic effects. Further research will address the relative importance of these agents in various cannabis preparations.
About the author:
Dr. Ethan Russo is a board-certified neurologist, who serves as Senior Medical Advisor to GW Pharmaceuticals. He is a past chairman of the International Association for Cannabinoid Medicines, and is the current president of the International Cannabinoid Research Society.
Fischedick, J. T., Hazekamp, A., Erkelens, T., Choi, Y. H. & Verpoorte, R. (2010). Metabolic fingerprinting of Cannabis sativa L., cannabinoids and terpenoids for chemotaxonomic and drug standardization purposes. Phytochemistry, 71, 2058-73.
Izzo, A. A., Borrelli, F., Capasso, R., Di Marzo, V. & Mechoulam, R. (2009). Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci, 30, 515-27.
Russo, E. B. (2007). History of cannabis and its preparations in saga, science and sobriquet. Chemistry & Biodiversity, 4, 2624-2648.
Cannabis oil: What is the best and healthiest way to produce cannabis oil?
by Dr Arno Hazekamp
What is Cannabis oil?
Concentrated cannabis extracts, also known as Cannabis oils because of their sticky and viscous appearance, are increasingly mentioned by self-medicating patients as a cure for cancer. In general, preparation methods for Cannabis oil are relatively simple and do not require particular instruments. The purpose of the extraction, often followed by a solvent evaporation step, is to make cannabinoids and other beneficial components such as terpenes available in a highly concentrated form. Cannabis oil is usually taken orally, by ingesting a small number of drops several times a day. Please find here some information on the question whether cannabis can cure cancer.
How is Cannabis oil prepared?
Various methods have been described for the preparation of Cannabis oil. The most popular method, as described by former (skin)cancer patient Rick Simpson from Canada, suggests the use of naphtha or petroleum ether as a solvent for the extraction. Following the success of Simpson oil, a number of related recipes have sprung up, emphasizing small but significant changes to the original recipe. Examples include focusing on safer solvents such as ethanol, or preventing exposure to organic solvents altogether, by using olive oil.
What is naphtha or petroleum-ether?
In general, petroleum-ether and naphtha refer to very similar products, even though different names may be used around the world; e.g. in some countries naphtha is equivalent to diesel or kerosene fuel. Both solvents are a mixture of petroleum hydrocarbons (PHCs), often available in a wide range of qualities. All the solvent components should be considered harmful and flammable, and some of them, such as hexane and benzene, may be neurotoxic. Both naphtha and petroleum-ether are considered potential cancer hazards according to their manufacturers. Moreover, products sold as naphtha may contain added impurities (e.g. Coleman® fuel) which may have harmful properties of their own.
Are residual solvents a health risk?
Although Cannabis oils are usually concentrated by evaporating the solvents that were used for extraction, this does not completely eliminate residual solvents. As a result of sample viscosity, the more concentrated an extract becomes, the more difficult it will be to remove the residual solvent from it. In such a case, applying more heat will increase solvent evaporation, but simultaneously more beneficial components (such as cannabinoids or terpenes) may be lost as well. The use of non-toxic solvents should therefore always be advised, so that potential residues are not harmful to health.
What is the best and healthiest way to prepare Cannabis oil?
Recently, an analytical study was performed to compare several generally used preparation methods on the basis of cannabinoids, terpenes, and residual solvent components. Solvents tested included ethanol, naphtha, petroleum-ether, and olive oil. Based on this study, the following recommendations can be made:
- As extraction solvents, ethanol and olive oil were shown to perform the best, extracting the full range of terpenes and cannabinoids present in cannabis plant material very efficiently. Additionally these solvents are safe for consumption.
- Unfortunately, pure ethanol also extracts large amounts of chlorophyll from cannabis material, which will give the final extract a distinct green, and often unpleasant, taste. Removing chlorophyll by filtering the ethanol extract over activated charcoal was found to be effective, but it also removed a large proportion of cannabinoids and terpenes, and is therefore not advised. Additionally, in many countries consumption-grade ethanol is an expensive solvent, as a result of added tax on alcohol products.
- Of the solvents tested, this leaves olive oil as the most optimal choice for preparation of cannabis oil for self-medication. Olive oil is cheap, not flammable or toxic, and the oil needs to be heated up only to 100°C (by placing a glass jar containing the product in boiling water for 1-2 hours) so no overheating of the oil can occur. After cooling down and filtering the oil it is immediately ready for consumption. As a trade-off, however, olive oil extract cannot be concentrated by evaporation, which means patients will need to consume a larger volume of it in order to get the same therapeutic results.
- Preheating of cannabis to ‘activate’ (decarboxylate) the cannabinoids may result in loss of terpenes as a result of evaporation. If the full range of terpenes is desired in the final Cannabis oil, dried buds and leaves can be used directly for extraction, without preheating.
About the author
Dr Arno Hazekamp is a phytochemical researcher at the Department of Plant Metabolomics of Leiden University, The Netherlands. He also coordinates the R&D program at Bedrocan BV.
Cancer: Do cannabinoids cure cancer?
by Dr Manuel Guzmán
Cannabinoids, the active components of cannabis and their derivatives, exert palliative effects in cancer patients by preventing nausea, vomiting and pain and by stimulating appetite. In addition, these compounds inhibit the growth of tumour cells in laboratory animals -mice and rats. However, at the moment there is not solid evidence to prove that cannabinoids –whether natural or synthetic- can effectively treat cancer in patients, although research is ongoing around the world.
Comprehensive FAQ sections -including scientific references- on cannabinoids and cancer can be found at the Cancer Research UK website and the National Cancer Institute of the US website. Here that information is summarized and discussed.
What is cancer?
Cancer is a broad term used for diseases in which abnormal cells divide without control and are usually able to invade other tissues, causing metastases and high rates of mortality and morbidity. Cancer is not just one disease but many diseases: more than 100 different cancers are well-typified from a histopatological point of view by the WHO and, most likely, there are hundreds if not thousands types of cancers according to molecular and genetic profiling.
Most cancers are named for the organ or type of cell in which they start. In addition, cancer types are usually grouped into the following broader categories:
- Carcinoma: cancer that begins in the skin or in tissues that line or cover internal organs.
- Sarcoma: cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.
- Leukaemia: cancer that starts in blood-forming tissues such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood.
- Lymphoma and myeloma: cancers that begin in the cells of the immune system.
- Central nervous system cancers: cancers that begin in the tissues of the brain and spinal cord.
Conclusion: Cancer is a very serious and heterogeneous disease, so fighting it therapeutically remains an extremely difficult challenge. Cannabinoids might therefore exert beneficial effects in some cancers but not in others.
Do cannabinoids inhibit cancer growth? (Laboratory research)
Virtually all the research into cannabinoids and cancer cells has been conducted so far using cancer cells grown in the lab or in animal models. Many scientific studies have reported that various cannabinoids (both natural and synthetic) exert a wide range of growth-inhibiting effects on cancer cells, including:
- Triggering cell death, through a mechanism called apoptosis.
- Stopping cells from dividing.
Preventing new blood vessels from growing into tumours –a process termed angiogenesis.
- Reducing the chances of cancer cells to metastasize through the body, by stopping cells from moving or invading neighbouring tissue.
- Speeding up the cell’s internal ‘waste disposal machine’ –a process known as autophagy
- which can lead to cell death.
Conclusion: Cannabinoids are efficacious drugs to treat at least some types of cancers in laboratory animals –mice and rats.
Do cannabinoids inhibit cancer growth? (Anecdotal evidence in humans)
As mentioned above, basically all the research investigating whether cannabinoids can treat cancer has been done in the lab. It is therefore important to be very cautious when extrapolating these results up to real live patients, who are a lot more complex than a Petri dish or a mouse. Anecdotal reports on cannabis use have been historically helpful to provide hints on the biological processes controlled by the endocannabinoid system and on the potential therapeutic benefits of cannabinoids. In the precise case of cancer there is a notable presence of videos and reports on the internet arguing that cannabis can cure cancer. These anecdotal claims may be completely or partially true in some cases, but overall remain –at least to date- weak and obscure. For example:
- We do not know whether the (supposed) effect of cannabis was due to a placebo effect.
- We do not know whether the tumour has (supposedly) stopped growing by natural/endogenous reasons -some tumours regress spontaneously/owing to the body’s anti-tumour defences.
- We do not know how many patients have taken cannabis and have not obtained any therapeutic benefit, that is, what is the (supposed) efficacy of the cannabis-based therapy.
- As most likely patients have gone through standard therapy prior to or concomitantly with cannabis use, we do not know whether the (supposed) effect of cannabis was in fact due -at least in part- to the standard therapy -perhaps enhanced by cannabis, but we have no proof.
- We do not know what are the parameters of tumour progression that have been monitored and for how long the patient has been monitored -many potentially beneficial effects of antineoplastic drugs (or of cannabis in this case) are just short-term actions, but what about long-term progression-free survival and overall survival?
- Cancer is a very heterogeneous disease, and so far none has put together a sufficient number of patients for a particular type of cancer to support that cannabinoids are efficacious drugs in that precise cancer.
Conclusion: Although it is possible –and of course desirable- that cannabis preparations have exerted some antineoplastic activity in some particular cancer patients, the current anecdotal evidence reported on this issue is pretty poor, and, unfortunately, remains far from supporting that cannabinoids are efficacious anticancer drugs for large patient populations.
Do cannabinoids inhibit cancer growth? (Clinical research)
Results have been published from only one Phase I clinical trial testing whether cannabinoids can treat cancer in patients. Nine people with advanced, recurrent glioblastoma multiforme –an aggressive brain tumour– that had previously failed standard therapy were given highly purified THC through a catheter directly into their brain. Under these conditions cannabinoid delivery was safe and could be achieved without significant unwanted effects. In addition, although no statistically-significant conclusions can be extracted from such a small cohort of patients and without a control group, the results obtained suggested that some patients responded -at least partially- to THC treatment in terms of decreased tumour growth rate, as evaluated by imaging and biomarker analyses. These findings were encouraging and substantially reinforced the interest on the potential use of cannabinoids in cancer therapies. However, they also highlighted the need for further research aimed at optimizing the use of cannabinoids in terms of patient selection, combination with other anticancer agents and use of other routes of administration.
Conclusion: There are still many unanswered questions around the potential for using cannabinoids as anticancer drugs, and it is necessary and desirable that exhaustive clinical studies are conducted to determine how cannabinoids can be used, other than for their palliative effects, to treat cancer patients.
About the author
Dr Manuel Guzman is professor at the Department of Biochemistry and Molecular Biology at Complutense University in Madrid, Spain. He coordinates the Cannabinoid Signaling Group.
Schizophrenia: Does cannabis use increase the risk for schizophrenia?
by Franjo Grotenhermen
The use of cannabis may be a risk factor for the development of schizophrenia, a type of psychosis. It is currently assumed that cannabis doubles the risk (or increases the risk by 2) if heavily used in adolescence. There are other factors that increase schizophrenia risk. For example having grown up in a big city also increases the risk by about 2 compared to having grown up in the countryside. This small increase in risk means that 1 to 2 out of 100 heavy cannabis users and 1 to 2 out of 100 city dwellers will develop schizophrenia during their lifetime, compared to 0.5 to 1 out of 100 people without any risk factor.
What is psychosis?
Psychosis is a serious medical condition of unknown origin. It refers to an abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality". The term “psychosis” is most often used as an “umbrella term” instead as a distinct diagnosis. People suffering from psychosis are described as psychotic. Psychosis is given to the more severe forms of psychiatric disorder, during which hallucinations and delusions and impaired insight may occur. Although there are drugs available that can ameliorate some of the symptoms, the disorder can not be cured. Schizophrenia is a special form of a psychotic disorder.
What is schizophrenia?
Schizophrenia is a mental disorder characterized by a breakdown of thought processes and by poor emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid beliefs, or disorganized speech and thinking. Hallucinations are perceptions in a conscious and awake state in the absence of external stimuli, which have qualities of real perception. For example, schizophrenics may hear voices in the absence of any voices. Beliefs, which are called delusions, are associated with strong conviction despite evidence to the contrary. For example, somebody may believe that he is an important historical personality such as Jesus or Napoleon. Often deficits of normal emotional responses are associated such as flat or blunted affect and emotion, poverty of speech, inability to experience pleasure, and lack of motivation. Depending on the clinical symptomatology schizophrenia can be classified in different subtypes.
How prevalent is schizophrenia?
About 15 to 20 new cases per 100.000 inhabitants of Western countries develop schizophrenia every year. The onset of symptoms typically occurs in young adulthood between the age of 18 and 35, and about 0.5 to 1.0 per cent of all citizens of Europe and North America develop schizophrenia during their lifetime. Delusions, thought disorders (e.g. thought broadcasting), and acoustic hallucinations are preliminary employed in diagnosis. These symptoms are often highly dramatic and dangerous, but these so-called “positive symptoms” normally improve over the years. On the other hand, the “negative symptoms” such as depression, inability to make social contacts, impoverishment of feelings often remain, resulting in psychosocial problems and unemployment.
What causes schizophrenia?
Both genes and the environment play a role in the development of schizophrenia. Certain variants of genes are associated with a higher risk of schizophrenia. This may explain, why schizophrenia is observed more often in some families compared to others. However, these genetic variants do not cause the disease, but play a role in the disposition to the disease. Somebody, who has a first-degree relative (parents, brother, sister) with schizophrenia, has a risk of 6.5 per cent to also develop the disease during lifetime. This means that of 100 first-degree relatives of people with schizophrenia 6 to 7 also develop the disease.
Environmental risk factors that have been established are pregnancy complications including stress, infections and malnutrition of the mother, birth complications, growing up in a large city, low but normal IQ (intelligence quotient), and drug consumption including cannabis use. Other factors, which may play an important role, are social isolation, family dysfunction and other heavily distressing factors. People with schizophrenia in the northern hemisphere are more likely to have been born in winter or spring compared to summer and autumn.
How to prevent schizophrenia?
Since risk factors are only associated with a relatively low increase of risk, they cannot be used for early detection and prevention of schizophrenia (Klosterkötter 2008). On the other hand, it is desirable to detect schizophrenia at an early stage, since early detection and early treatment is associated with a more favourable course of the disease, less depression and less suicide. Thus, prevention efforts and programs are concentrated on the detection of risk symptoms during the so-called prodromal state (early warning signs) and on making a correct diagnosis after outbreak of the disease as early as possible.
In about three quarters of all cases the outbreak of schizophrenia is preceded by a prodromal state for an average of five years. During this period the person may have thought disturbances, unusual experiences of perception, paranoid ideas, decreased ability to discriminate between ideas and perception, fantasy and true memories, and similar symptoms several times a week. There is a high risk for people experiencing prodromal symptoms to develop psychotic symptoms and psychotic episodes finally leading to schizophrenia.
What is the role of cannabis in the development of schizophrenia?
In a review of seven longitudinal studies on the association between cannabis use and schizophrenia researchers found that individuals who had ever used cannabis had an increased risk of psychosis or psychotic symptoms of 41 per cent compared to individuals who had never used cannabis. In longitudinal studies a large number of people are followed for several years, ideally from birth to adulthood, to identify for example causes of diseases or protective factors against diseases. Frequent cannabis users had twice the risk of non-users (odds ratio: 2.09) (Moore et al. 2007). Researchers noted that the uncertainty about whether cannabis causes psychosis is unlikely to be resolved by further longitudinal studies. It is most likely that cannabis use precipitates schizophrenia in individuals who are vulnerable because of a personal or family history of schizophrenia (Degenhardt and Hall 2006).
It is difficult to prove that cannabis is indeed a causal factor in the development of schizophrenia, since the association may be non-causal, at least in part. For example, some people with schizophrenia may self-medicate with cannabis to treat some of their symptoms, especially negative symptoms. However, there is increasing evidence from long-term epidemiological studies that cannabis plays a causal role.
What is the role of cannabinoids in the treatment of schizophrenia?
There are two published case series, which demonstrate that cannabis or THC may be of therapeutic value in some cases of schizophrenia, who do not respond to conventional medication (Schwarcz et al. 2009, Schwarcz et al. 2010). The authors of these reports assume that with regard to brain physiology the cause of schizophrenia in these patients may differ from other patients with schizophrenia, who respond to conventional anti-psychotic medication, that these patients may suffer from low endocannabinoid brain function.
There is clinical evidence that the natural plant cannabinoid cannabidiol (CBD) at a daily dose of 800 mg may be as effective as conventional medication in the treatment of schizophrenia (Leweke et al. 2012). CBD is known to decrease or abolish the psychological effects of THC. The treatment with CBD is associated with an increase in anandamide blood levels, and this increase is thought to be responsible for symptom improvement.
About the author
Dr Franjo Grotenhermen is chairman of the German Association for Cannabis as Medicine (ACM) and executive director of the International Association for Cannabinoid Medicines (IACM). He is working for the nova-Institut in Huerth/Rhineland, Germany.
Anxiety: Does cannabis cause anxiety or does it reduce anxiety or may both occur?
US Institute of Medicine
Although euphoria is the more common reaction to smoking marijuana, adverse mood reactions can occur. Such reactions occur most frequently in inexperienced users after large doses of smoked or oral marijuana. They usually disappear within hours and respond well to reassurance and a supportive environment. Anxiety and paranoia are the most common acute adverse reactions, others include panic, depression, dysphoria, depersonalization, delusions, illusions, and hallucinations.
Source: Joy JE, Watson SJ, Benson JA, eds. Marijuana and medicine: Assessing the science base. Institute of Medicine. Washington DC: National Academy Press, 1999.
US Institute of Medicine
The 'high' associated with marijuana is not generally claimed to be integral to its therapeutic value. But mood enhancement, anxiety reduction, and mild sedation can be desirable qualities in medications particularly for patients suffering pain and anxiety. Thus, although the psychological effects of marijuana are merely side effects in the treatment of some symptoms, they might contribute directly to relief of other symptoms.
Source: Joy JE, Watson SJ, Benson JA, eds. Marijuana and medicine: Assessing the science base. Institute of Medicine. Washington DC: National Academy Press, 1999.
Giovanni Marciano and colleagues
Here we show that the endogenous cannabinoid system has a central function in extinction of aversive memories. (…) Mice were trained to associate a tone with an electric footshock (conditioning). After conditioning, animals shivered when they heard the tone. This response served as an indicator of aversive memory, and is gradually extinguished on repeated tone presentations. (...) Mice without cannabinoid-1 receptors showed strongly impaired short-term and long-term extinction of the aversive memory (...).
Overall our findings suggest that the endogenous cannabinoid system could represent a therapeutic target for the treatment of diseases associated with inappropriate retention of aversive memories or inadequate response to aversive situations, such as posttraumatic stress disorders, phobia, and certain forms of chronic pain.
Modified according to: Marsicano G, et al. The endogenous cannabinoid system controls extinction of aversive memories. Nature 2002;418(6897):530-534.
Marciano and colleagues propose a new role for this endocannabinoid system - extinguishing fear-related memories in mice. The finding might have implications for treating anxiety disorders in humans.
We can form memories in several different ways, one of which is Pavlovian conditioning - the classic example being that of Pavlov's dogs, which learned to expect food whenever they heard a ringing tone. We all form these types of associations; for instance, we may associate a particular piece of music with our first love affair. But the connection need not always be pleasant. Imagine you are having a quiet walk in a park when you are threatened by an armed person. During the attack you are terrified; your heart races and your palms are sweaty. You run and escape. Later, you may find that entering the same park brings back in detail the memory of attack, right down to the sweaty palms. (...)
It has been argued that the neuronal circuitry underlying fear conditioning has similarities to that responsible for fear-related clinical conditions, such as post-traumatic stress disorder. Behavioural therapies for these conditions - including systematic desensitization and imagery therapies - share features with extinction. The finding that the endocannabinoids contribute to extinction raises the possibility that drugs that target these molecules and their receptors could be useful new treatments for anxiety disorders. Finally there is much anecdotal evidence of patients using cannabis heavily in the early stages of psychiatric illness. This has often been thought to contribute to acute illness. But it seems possible that it may instead be a form of self-medication for the sometimes extreme anxiety that these people experience.
Source: Sah P. Neurobiology: Never fear, cannabinoids are here. Nature 2002;418(6897):488-9.
I would like to present a case of successful cannabis use in panic attacks. A Swiss who was suffering from panic attacks recently reported me, that cannabis use was very helpful for him between the attacks. He had not used cannabis during the attack since it would be too late then.
The attacks had started about nine months ago without recognizable cause and occured nearly daily. He also suffered from nausea, loss of appetite and dizziness. He had been prescribed strong medical drugs from his doctor, which he would not like to take permanently. Five months ago he started to use cannabis, which he takes about three times a week now. The panic attacks declined in frequency and intensity. Dizziness and nausea have disappeared completely and he regained appetite. The panic attacks nearly disappeared as well.
Source: Grotenhermen F. Kann Cannabis bei einer aufkommenden Panikattacke sinnvoll eingesetzt werden? [Can cannabis be used in an arising panic attack?] Hanf-Magazin, September 2002.
Rare vegetative side effects: Can increased blood pressure, headache, chills, nausea, and belly ache be ascribed to cannabis use?
Cannabis exerts manifold effects on the vegetative nervous system, among them increased heart rate, dry mouth, slowdown of intestinal movements, changes of blood pressure (decrease and increase). These effects are usually mild and well tolerated. Their intensity varies from person to person. In some subjects an unusual intensity of these side effects and unusual kinds of vegetative side effects have been observed, Among them strong increase of heart rate, strong increase of blood pressure, shivering and chills, bellyache, headache, nausea and vomiting.
The following experiences were told to me by recreational users: A young man who had used cannabis for many years without relevant side effects experienced strong headache after the use of LSD which made him to attend a hospital. A high blood pressure (systolic pressure of 190 mmHg) was measured. Later every use of cannabis also resulted in headache and significant increase of blood pressure. Another user reported signficant and frightening increase of heart rate (140 beats per minute) lasting for more than one hour occuring sometimes after use of the drug. Two cannabis users reported of bellyache within a few minutes after smoking of whom one experienced flatulences. Another user experienced chills and shivering every time he used the drug. In the internet (http://rxmarijuana.com) I found the report of a man who complained of several symptoms, significant increase of heart rate, anxiety, painful belching, and chills.
Adverse experiences information summarized in the tables below was derived from well-controlled clinical trials conducted in the US and US territories involving 474 patients exposed to Marinol (dronabinol). Studies of AIDS related weight loss included 157 patients receiving dronabinol at a dose of 2.5 mg twice daily and 67 receiving placebo. Studies of nausea and vomiting related to cancer chemotherapy included 317 patients receiving dronabinol and 68 receiving placebo. A cannabinoid dose-related "high" (easy laughing, elation and heightened awareness) has been reported by patients receiving Marinol in both the antiemetic (24%) and the lower dose appetite stimulant clinical trials (8%).
The most frequently reported adverse experiences in patients with AIDS during placebo-controlled trials involved the CNS [central nervous system] and were reported by 33% of patients receiving Marinol. About 25% of patients reported a minor CNS adverse event during the first 2 weeks and about 4% reported such an event each week for the next 6 weeks thereafter.
PROBABLY CAUSALY RELATED: Incidence greater than 1%.
Rates derived from clinical trials in AIDS-related anorexia [appetite loss] (N=157) and chemotherapy-related nausea (N=317). Rates were generally higher in the anti-emetic use (given in parenthesis). [Explanation of technical terms in square brackets].
Body as a whole: Asthenia [loss or lack of strength or energy].
Cardiovascular [related to heart and circulation]: Palpitation [uneasy awareness of the heart beat], tachycardia [fast heart rate], vasodilation/facial flash.
Digestive [related to digestion]: Abdominal pain, nausea, vomiting.
Nervous system: (Amnesia), anxiety/nervousness, (ataxia [disturbance of muscle coordination]), confusion, depersonalization, dizziness, euphoria, (hallucination), paranoid reaction, somnolence, thinking abnormal.
PROBABLY CAUSALY RELATED: Incidence less than 1%.
Event rates derived from clinical trials in AIDS-related anorexia (N=157) and chemotherapy-related nausea (N=317).
Cardiovascular: Conjunctivitis [reddening of the eye], hypotension.
Digestive: Diarrhea, fecal incontinence.
Musculosceletal: Myalgia [pain in the muscles].
Nervous system: Depression, nightmares, speech difficulties, tinnitus [ear noise].
Skin and Appendages [hair and nails]: Flushing.
Special senses: Vision difficulties.
CAUSALY RELATIONSHIP UNKNOWN: Incidence less than 1%.
The clinical significance of the association of these events with Marinol treatment is unknown, but they are reported as alerting information for the clinician.
Body as a whole: Chills, headache, malaise.
Digestive: Anorexia, hepatic enzyme elevation.
Respiratory: Cough, rhinitis, sinusitis.
Skin and Appendages: Sweating.
Source: Information on Marinol (dronabinol, THC), Unimed Pharmaceuticals, Inc., January 2001, www.marinol.com (physicians information).
Gastric ulcer: Can cannabis be helpful in gastric ulcers?
There are no clinical studies with cannabinoids in gastric ulcers. However, THC and other substances that bind to the cannabinoid-1-receptor (CB1 receptor agonists) inhibited the gastric acid production in humans and the formation of ulcers in animals.
The nervous system of the bowel of several species, including the mouse, rat, guinea pig and humans, contains cannabinoid CB1 receptors that depress motility of stomach and intestine. (...)
Gastric acid secretion is also inhibited in response to CB1 receptor activation, although the detailed underlying mechanism has yet to be elucidated. Cannabinoid receptor agonists delay gastric emptying in humans as well as in rodents and probably also inhibit human gastric acid secretion. (...)
The extent to which the effects on gastrointestinal function of cannabinoid receptor agonists or antagonists/inverse agonists can be exploited therapeutically has yet to be investigated as has the extent to which these drugs can provoke unwanted effects in the gastrointestinal tract when used for other therapeutic purposes.
Modified according to: Pertwee RG. Cannabinoids and the gastrointestinal tract. Gut 2001;48(6):859-867.
Adami et al.
In anaesthetized rats the non selective CB-receptor agonist WIN 55,212-2 and the selective CB(1)-receptor agonist HU-210 dose-dependently decreased the acid secretion. (...) Our results indicate that the antisecretory effects of cannabinoids on the rat stomach are mediated by suppression of the activity of the vagus nerve on the stomach through activation of CB1 receptors.
Modified according to: Adami M, et al. Gastric antisecretory role and immunohistochemical localization of cannabinoid receptors in the rat stomach. Br J Pharmacol 2002;135(7):1598-1606.
Sofia et al.
Delta-9-tetrahydrocannabinol (THC) inhibited ulcer formation in the rat. However, this antiulcer activity of THC was substantially less than for tridihexethyl chloride.
Modified according to: Sofia RD, et al. Evaluation of antiulcer activity of delta9-tetrahydrocannabinol in the Shay rat test. Pharmacology 1978;17(3):173-177.
Nalin et al.
In 90 volunteers participating in a vaccine-development programme consumption of beer more than 3 days a week was linked with high stomach acid output, and smoking of cannabis greater than 2 days a week was linked with low acid output.
Source: Nalin DR, et al. Cannabis, hypochlorhydria, and cholera. Lancet 1978;2(8095):859-862.
THC in blood: How long can THC and his metabolites be detected in blood?
With usual tests 0.5 nanograms per milliliter (ng/ml) of THC and 0.5 ng/ml of its metabolite THC-COOH can be detected in blood plasma. The time until falling short of this detection limit after consumption varies considerably, even if the same amount of THC was ingested.
After smoking a low dose cannabis cigarette (about 16 mg THC) the detection limit of 0.5 ng/ml THC in plasma was reached after 7.2 hours on average (range: 3-12 hours) and following a high dose cigarette (about 34 mg THC) a plasma concentration of 0.5 ng/ml THC was reached within 12.5 hours (range: 6-27 hours). The metabolite THC-COOH was detectable for a considerably longer time, for 3,5 days (range: 2-7 days) after the low dose and for 6,3 days (range 3-7 days) after smoking the high dose cigarette.
The elimination half life for THC metabolites from plasma is longer than the elimination half life of the THC itsself. With regular use THC-COOH may be detectable in the plasma for several weeks.
Modified according to: Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokin 2002, in press.
Children: What is known about the medical use of cannabis in children?
There are only two clinical studies with cannabinoids in children, one with delta-8-THC and the other with the THC derivative nabilone, both investigating their benefits in side effects of cancer chemotherapy. Probably due to a different distribution of cannabinoid receptors in the brains of adults and children, children seem to tolerate relatively high doses without relevant psychic effects. To my knowledge cannabis or dronabinol (THC) is primarily used in neurological disorders, such as epilepsy, drowning accident, hyperactive disorders, etc.
An American judge has allowed the mother of a hyperactive child to carry on giving him cannabis. The judge dismissed a petition by social services to remove the child from his mother's home in Rocklin, California. The eight-year-old has a severe mental disorder. His mother gives him cannabis because she says conventional medicine doesn't work. Child Protective Services had accused her of being an unfit mother after learning of the treatment. The mother turned to cannabis after a paediatrician suggested she give it a try, and she reports her son's behaviour improved markedly, his mood swings levelled off and he developed friendships with other children. Initially, the mother prepared the boy's "medicine" in the form of muffins, which she fed him regularly. WENN via COMTEX of 6 December 2001
Abrahamov and colleagues
Delta-8-tetrahydrocannabinol (delta-8-THC), a cannabinoid with lower psychotropic potency than the main Cannabis constituent, delta-9-tetrahydrocannabinol (delta-9-THC), was administered to eight children, aged 3-13 years with various cancers of the blood, treated with different anticancer drugs for up to 8 months. The dose was 18 mg oral THC per square meter of body surface in edible oily drops. (The body surface of a child of 30 kilos is about one square meter, the one of an adult of 75 kilos about 1.8 square meter). The total number of treatments with delta-8-THC so far is 480. The THC treatment started two hours before each anticancer treatment and was continued every 6 hrs for 24 hours. Vomiting was completely prevented. The side effects observed were negligible.
Modified according to: Abrahamov A, Abrahamov A, Mechoulam R. An efficient new cannabinoid antiemetic in pediatric oncology. Life Sciences 1995;56(23-24):2097-2102.
Dalzell and colleagues
A trial was conducted comparing the new synthetic cannabinoid nabilone with oral domperidone (an antiemetic drug) in a group of children receiving repeated identical courses of chemotherapy for a variety of cancers. Eighteen of 23 children, aged 10 months to 17 years, completed the trial. When taking nabilone they experienced significantly fewer vomiting episodes and less nausea, and two thirds preferred nabilone. The most common side effects of treatment with nabilone were somnolence and dizziness, with one patient being disturbed by hallucinations. The results indicate that nabilone is an effective antiemetic for children having chemotherapy, even for young children. It seems to be superior in this respect to domperidone, and although side effects occur more often, these are mostly acceptable to patients. It can be recommended as an alternative to conventional antiemetic treatment throughout childhood.
Modified according to: Dalzell AM, Bartlett H, Lilleyman JS. Nabilone: an alternative antiemetic for cancer chemotherapy. Archives of Disease in Childhood 1986;61(5):502-505.
Detection of cannabis consumption: Can the use of cannabis be detected in blood or urine with routinely laboratory tests?
The use of cannabis or THC in blood, urine or other body fluids can only be detected through specific search for THC or its metabolites. The search for THC or its metabolites is not a usal part of routinely blood or urine tests performed in a medical practice or in a hospital.
If possible, slowly increasing doses should be applied in a titrated fashion to avoid undesirable side effects on psyche and circulation. Starting doses are 2 x 2.5 mg or 2 x 5.0 mg of dronabinol per day. Dosages may be increased up to several units of 10 mg daily. In appetite loss and nausea due to AIDS 5-20 mg THC daily are usually sufficient, pain treatment may often need higher doses. If natural cannabis products of unknown THC content are used orally, the patient should begin with about 0.05-0.1 grams of the drug (for cannabis with an average THC content of 5 percent this corresponds to 2.5-5 mg THC). If the THc content is unknown, a store of cannabis sufficient for several weeks should be layed in so that a constant quality is ensured. In a study by Fairbairn and colleagues (1976) the THC content of marijuana only decreased by 7% within 47 weeks with dark, dry storage at 5°C, and by 13% at a temperature of 20°C.
To achieve reproducible effects cannabis or THC should be ingested always under similar conditions with regard to food intake, e.g. always one hour before a meal. If natural cannabis preparations are used doses should be weighed carefully and taken with the same carrier, e.g. cannabis tea with half a gram of dried cannabis flowers on half a liter of water and some cream.
As with opiates, some side effects may decrease within some days or weeks, thereby increasing the acceptance of the drug. Prolonged THC ingestion causes tolerance to unwanted effects on circulation and to psychological effects, so that daily doses of more than 50 mg THC may sometimes be taken without significant unwanted psychic or physical side effects. Heavy regular users in western societies may smoke five to ten cannabis cigarettes per day or more, thus well tolerating daily doses of 100 mg THC and more. In a sample of cannabis users analyzed by Solowij (1991) mean weekly consumption was 766 mg THC, ranging from 30-2400 mg THC.
Tolerance may also arise with respect to therapeutically desired effects (e.g. decrease of intraocular pressure, pain reduction), and require increased doses after some time of treatment.
Modified according to: Grotenhermen F. Harm reduction associated with inhalation and oral administration of cannabis and THC. Journal of Cannabis Therapeutics 2001;1(3-4):133-152.
Cognitive performance: Does long-term use of cannabis impair intellectual ability?
Pope and colleagues
We recruited individuals aged 30 to 55 years in 3 groups: (1) 63 current heavy cannabis users who had smoked cannabis at least 5000 times in their lives and who were smoking daily at study entry; (2) 45 former heavy users who had also smoked at least 5000 times but fewer than 12 times in the last 3 months; and (3) 72 control subjects who had smoked no more than 50 times in their lives. Subjects underwent a 28-day abstinence from cannabis use, monitored by observed urine samples. On days 0, 1, 7, and 28, they completed a complex neuropsychological test battery.
Results: At days 0, 1, and 7, current heavy users scored significantly below control subjects on recall of word lists. By day 28, however, there were virtually no significant differences among the groups on any of the test results, and no significant associations between cumulative lifetime cannabis use and test scores.
Conclusion: Some cognitive deficits appear detectable at least 7 days after heavy cannabis use but appear reversible and related to recent cannabis exposure rather than irreversible and related to cumulative lifetime use.
Modified according to: Pope HG Jr, et al. Neuropsychological performance in long-term cannabis users. Arch Gen Psychiatry 2001 Oct;58(10):909-15.
Peter Fried and colleagues
We determined marijuana use for seventy 17- to 20-year-olds whose intelligence quotient (IQ) had been determined at the age of 9-12 years. The IQ difference scores were calculated by subtracting each person's IQ score at 9-12 years (before initiation of drug use) from his or her score at 17-20 years. We then compared the difference in IQ scores of current heavy users (at least 5 joints per week), current light users (less than 5 joints per week), former users (who had not smoked regularly for at least 3 months) and non-users (who never smoked more than once per week and no smoking in the past two weeks).
Results: Current marijuana use was significantly correlated in a dose-related fashion with a decline in IQ over the ages studied. The comparison of the IQ difference scores showed an average decrease of 4.1 points in current heavy users compared to gains in IQ points for light current users (5.8), former users (3.5) and non-users (2.6).
Interpretation: Current marijuana use had a negative effect on global IQ score only in subjects who smoked 5 or more joints per week. A negative effect was not observed among subjects who had previously been heavy users but were no longer using the substance. We conclude that marijuana does not have a long-term negative impact on global intelligence. Whether the absence of a residual marijuana effect would also be evident in more specific cognitive domains such as memory and attention remains to be ascertained.
Modified according to: Fried P, et al. Current and former marijuana use: preliminary findings of a longitudinal study of effects on IQ in young adults. CMAJ 2002;166(7):887-91.
Nadia Solowij & Brin Greyner
Cannabis exerts its most prominent effects on the central nervous system (CNS), whether smoked or ingested. It is primarily for its mind altering or psychoactive properties that it is used recreationally in many parts of the world. Human studies of the acute effects of cannabis suggest that the cannabinoid receptor system may be involved in regulating mood, emotion, attention, memory and many other cognitive functions. What is not yet certain is the extent to which any of these functions, and indeed the endogenous cannabinoid system and receptor itself, are affected by the prolonged use of exogenous cannabinoids. The evidence to date from both human and animal research suggests that they are not grossly impaired in the long term but that there are alterations in their function. (…)
It is not clear to what extent the cognitive and psychological effects of long term cannabis use might impact upon daily life, although cannabis users themselves complain of problems with memory, concentration, loss of motivation, paranoia, depression, dependence and lethargy. Schwenk (1998) has argued that there is no clear causal relationship between cannabis use and job performance. The nature of the cognitive deficits as assessed by psychological testing suggests that long term users would perform reasonably well in routine tasks of everyday life, although they may be more distractible. Difficulties are likely to be encountered in performing complex tasks that are novel or that cannot be solved by automatic application of previous knowledge, or with tasks that rely heavily on a memory component or require strategic planning and multi-tasking. (…) The extent to which the subtle cognitive impairments may recover following cessation of use is also unknown, but research is in progress.
Solowij N, Greyner B. Long term effects of cannabis on psyche and cognition. In: Grotenhermen F, Russo E, eds. Cannabis and cannabinoids: pharmacology, toxicology and therapeutic potential. Binghamton, NY: Haworth Press, 2001, in press.
Lynn Zimmer & John Morgan
The cognitive process most clearly affected by marijuana is short-term memory. In laboratory studies, subject under the influence of marijuana have no trouble remembering things they learned previously. However, they display diminished capacity to learn and recall new information. This diminishment lasts for the duration on intoxication. There is no convincing evidence that heavy long-term marijuana use permanently impairs memory or other cognitive functions. (...)
During the past thirty years, researchers have found, at most, minor cognitive differences between chronic marijuana users and non-users, and the results differ substantially from one study to another. Based on this evidence, it does not appear that long-term marijuana use causes significant permanent harm to intellectual ability.
Zimmer L, Morgan JP. Marijuana Myths Marijuana Facts. A review of the scientific evidence. New York/San Francisco: The Lindesmith Center, 1997.
House of Lords (UK)
Cannabis can have untoward long-term effects on cognitive performance, i.e. the performance of the brain, particularly in heavy users. These have been reviewed for us by the Royal College of Psychiatrists and the Royal Society. While users may show little or no impairment in simple tests of short-term memory, they show significant impairments in tasks that require more complex manipulation of learned material (so-called "executive" brain functions). There is some evidence that some impairment in complex cognitive function may persist even after cannabis use is discontinued; but such residual deficits if present are small, and their presence controversial. Dr Jan van Amsterdam of the Netherlands National Institute of Public Health and the Environment, who has reviewed the literature on long-term cognitive effects of prolonged heavy use and kindly came to Westminster to tell us his findings, pointed out the practical difficulties of assessing possible residual effects. These include the impossibility of obtaining predrug baseline values (i.e. measures of the cognitive functioning of the subject before their first use of cannabis), the difficulty of estimating the drug dose taken, the need for a lengthy "washout" period after termination of use to allow for the slow elimination of residual cannabis from the body, and the possibility of confusing long-term deficits with withdrawal effects. He felt that many of the published reports on this subject had not taken adequate account of these problems.
House of Lords Select Committee on Science and Technology. Cannabis. The scientific and medical evidence. London: The Stationery Office, 1998.
Heating of cannabis: Why should cannabis products be heated before eating?
In the plant the cannabinoids exist mainly in their carboxylic forms as cannabinoid acids. However, the phenolic form of THC is responsible for the psychotropic and the most medicinal effects. Decarboxylation (separation of CO2) to the phenolic form occurs readily over time, upon heating or under alkaline conditions.
The ratio of THC acids (THCA) to phenolic THC has been reported to range between 2:1 (Africa) and >20:1 (Switzerland) in leaves and flowers of Cannabis sativa. In plants grown in Middle Europe (United Kingdom) from Moroccan, Sri Lankan and Zambian seed stocks the THCA/THC ratio was 17:1 compared with 2:1 in the plants from the original areas (Africa, Asia). In hashish (cannabis resin) the THCA/THC ratio was reported to range between 6.1:1 and 0.5:1, the latter in hashish from India. Thus, the percentage of phenolic THC of all THC in cannabis products varied between less than 5% in cannabis leaves grown in Switzerland up to 65% in hashish from India.
Cannabis products with a high content of phenolic THC (e.g. hashish) may be very potent without heating, but usually the potency of cannabis products is considerably increased with heating (smoking, cooking).
Modified according to: Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics 2001, in press.
Risks of smoking: What are the major strategies to reduce the risks of cannabis smoking?
Donald P. Tashkin
The smoke contents of marijuana are at least qualitatively similar to those of tobacco, with the major exception that marijuana smoke contains delta-9-tetrahydrocannabinol (delta-9-THC) and approximately 60 additional cannabinoid compounds not found in tobacco and that tobacco contains nicotine that is absent from marijuana. Many of the ingredients that are common to marijuana and tobacco smoke are known to be toxic to respiratory tissue. These toxic components include hydrocyanic acid, oxides of nitrogen, acrolein, reactive aldehydes and several known carcinogens. It is therefore reasonable to expect that repeated inhalation of the noxious components in cannabis smoke may have long-term adverse effects on the lung similar to those that have been observed in regular tobacco smokers.
Tashkin DP. Respiratory risks from marijuana smoking. Grotenhermen F, Russo E, eds. Cannabis and cannabinoids. Pharmacology, toxicology, and therapeutic potential. Binghamton NY: Haworth Press, 2001, in press.
The major strategies to reduce the risks of smoking are:
- The use of cannabis strains with high THC content. (...) - The use of pure cannabis. Sometimes cannabis is smoked together with tobacco or other dried herbs. This procedure should be avoided to minimize the inhalation of smoke from burnt plant material.
- The use of pipes. Pipes are superior to cigarettes in some situations in that they easily allow the patient to smoke small amounts of pure high-grade cannabis. The percentage of tars in the smoke is reduced by condensation on the pipe walls. Pipes should be cleaned frequently. Water pipes are inferior to cigarettes and should be avoided. (...)
- The use of cannabis that is free of natural contaminants and adulterants. Only disease-free cannabis should be harvested and air-dried. (...)
- The use of inhalation devices that reduce output of tars. (...) Gieringer tested vaporizers that heat marijuana to 180-190°C vaporizing THC below the burning point of cellulose and other plant material. The production of polycyclic hydrocarbons was reduced. The best vaporizer delivered 10 parts of tar to one part of cannabinoids, cannabis cigarettes yielded a ratio of 13:1 (average), and water pipes an average of 27:1 (...). Thus, the best vaporizers achieved a performance ratio about 25% higher than the unfiltered cannabis cigarette, while water pipes were less favorable than cigarettes. The use of a filter in a cannabis cigarette was not advantageous since it not only filtered the tars, but also the cannabinoids. Indeed, the performance ratio was decreased by about 30% compared to the unfiltered cigarette.
In a new study Gieringer was able to demonstrate that combustion products were substantially reduced by using another vaporizer. The used device produced THC at a temperature of 185°C while completely eliminating benzene, toluene and naphthalene. Significant amounts of benzene began to appear at temperatures of 200°C, while combustion occurred around 230°C or above. Traces of THC were in evidence as low as 140°C. Carbon monoxide and tars were both qualitatively reduced by the vaporizer, but were not quantificated in this study. However, a significant reduction of polycyclic aromatic hydrocarbons was assumed since vaporized cannabis emitted a thin gray vapor and the plant material was left with a green to greenish-brown "toasted" appearance, whereas the combusted sample produced thick smoke and turned to ash. (...)
- Combination of oral use and inhalation. In several indications, a combined regime of a basic oral medication with cannabis or THC and a demand inhaled medication may be useful to reduce risks from smoking and from possible overdosage with oral administration.
Grotenhermen F. Harm reduction associated with inhalation and oral administration of cannabis and THC. Journal of Cannabis Therapeutics 2001, in press.
Urine tests: How long can THC metabolites be detected in urine?
Ellis and colleagues
The urinary excretion patterns of 86 chronic cannabis users were examined after their last cannabis use by two common screening methods (...). We demonstrated that under very strictly supervised abstinence, chronic users can have positive results for cannabinoids in urine (...) for as many as 46 consecutive days from admission, and can take as many as 77 days to drop below the cut-off calibrator for 10 consecutive days. For all subjects, the mean excretion time was 27 days (...). Demographic, body type, and drug history variables proved to be only moderate predictors of excretion patterns."
Ellis GM Jr Mann MA Judson BA Schramm NT Tashchian A. Excretion patterns of cannabinoid metabolites after last use in a group of chronic users. Clin Pharmacol Ther 1985;38(5):572-578.
Excretion of THC and its metabolites in chronic users can be found in the range of 4-6 weeks. In the literature a 10 year long intensive cannabis use was reported to result in detection of use after 77 days with common tests. With single or occasional use excretion in urine is rarely short (some hours), usually it lasts for 3-5 days.
Aderjahn R. Toxikologischer Cannabisnachweis [Toxicological cannabis detection]. In: In: Berghaus G, Krüger HP, eds. Cannabis im Straßenverkehr [Cannabis in road traffic]. Stuttgart: Gustav Fischer, 1998.
Coleman en Baselt
OBJECTIVE: We have become aware of several commercial products that, when orally ingested, will purportedly not only eliminate "toxins" from a person's system, but will also correct any urinary imbalances caused by excessive water consumption. METHOD: Unblinded study of one volunteer subject, tested weekly x 4 for 24-hour urine elimination of test drug under conditions of control, control plus 1200 ml water, Quick Flush, and Eliminator. RESULTS: Each of the treatment protocols studied caused reductions of drug or metabolite concentrations as measured by gas chromatography-mass spectrometry in urine specimens (...), yet the radioimmunoassay screening results demonstrated very little effect. Water alone was approximately as effective as the two commercial products in reducing the metabolite level. None of the treatment protocols employed in this study altered urinary pH, specific gravity, or creatinine concentration outside the normally accepted physiological range. CONCLUSIONS: Attempts to conceal drug abuse by water dilution are most likely to play a substantial role when concentrations are at or near the detection threshold for a particular assay such as the terminal stages of drug eliminations. Coleman DE Baselt RC. Efficacy of two commercial products for altering urine drug test results. J Toxicol Clin Toxicol (1997) 35(6):637-642.
Cannabis tincture: How can I prepare a cannabis tincture or cannabis oil?
Old formulas on medicines of cannabis suggest the following procedure (if you have no special pharmaceutical equipment):
Cannabis tincture: Take about 3-5 parts of alcohol (e.g. brandy or ethyl alcohol from the pharmacy, 40-70%) and 1 part cannabis leaves/flowers (e.g. 25 g marijuana and 100 ml alcohol). Keep it in a dark and cool place for about 10 days. Shake it from time to time. Filter it using a sieve. Store the finished tincture dark and cold (e.g. in your refrigerator), so that efficacy will remain for several weeks and months.
Cannabis oil: Take some dried cannabis, reduce it to very small pieces, and add edible oil (e.g. olive oil) so that the plant material is completely covered with the oil. Keep it in a dark and cool place for about 3 weeks. Shake it a little every day. Filter it using a sieve. You may use this oil for internal and external application.
Dr. Fankhauser is a Swiss pharmacist.
José T. Gállego
It is easy to prepare a tincture or an oil from cannabis, that concentrates the active compounds of the plant. You need marijuana (any quality, good or bad, leaves or flowers), ethyl alcohol of 96-99% (e.g. from the pharmacy), a glass that can be closed (e.g. used for marmalade), a coffee filter or a piece of fabric (e.g. a part of a t-shirt), a deep plate or a frying pan, a bottle with a dropper.
Reduce the cannabis to small pieces and put it into the glass. Cover it with enough alcohol. Keep it in a dark and cool place for about a week. Shake it every day. Filter it using a coffee filter or the fabric. Press the last drops of alcohol out of the plant material. You may repeat this process several times, at least once, better two times: you may again put the cannabis into the glass and cover it with alcohol…. Finally, put all the alcohol (it will have a green colour) into to a deep plate. Keep it in a tempered and ventilated place so that some of the alcohol will be evaporated increasing the cannabinoids concentration of the tincture. This may take ten days. When enough alcohol is evaporated fill the extract into the bottle with the dropper.
The cannabis tincture can be used directly, or dissolved in a drink or food, or vaporized. To vaporize the tincture a commercial vaporizer or the old silver paper system can be used. Form a teaspoon out of silver paper, put some drops of the tincture on it, carefully heat it with a candle until the alcohol evaporates. Than inhale it using a small tube (e.g. the body of a ball point pen).
To produce hashish oil you have to evaporate all the alcohol from the tincture until the extract becomes a dark paste (similar to tar). It is possible to place the glass at a warm place to accelerate the process of evaporation. It should not be placed into the sun because the THC will be destroyed faster than. It should not be heated to avoid an explosion of the alcohol.
According to: Gállego JT: Tintura de cannabis. Canamo, No 46, July 2001:76-77.
Heart attack: Does cannabis use cause heart attacks?
- Angina = Feeling of discomfort in the chest or chest pain due to heart disease
- Beta-blockers = class of drugs used for the treatment of high blood pressure and heart diseases
- Coronary = with regard to the arteries of the heart
- Coronary disease (coronary heart disease) = narrowing of the arteries of the heart
- CRP (C-reactive protein) = indicator of inflammation
- Exercise time = Time in a stress test that tests heart function
- Longitudinal epidemiological studies = studies that follow a certain group of people (often several hundreds or thousands) for a long period of time to discover differences in subgroups, for example in dependency of life style and habits
- Myocardium = heart muscle
- Myocardial = with regard to the heart muscle
- Myocardial infarction = heart attack
Murray A. Mittleman and colleagues
We interviewed 3882 patients (1258 women) with acute myocardial infarction an average of 4 days after infarction onset. (...) Of the 3882 patients, 124 (3.2%) reported smoking marijuana in the prior year, 37 within 24 hours and 9 within 1 hour of myocardial infarction symptoms. (...) The risk of myocardial infarction onset was elevated 4.8 times over baseline (95% confidence interval, 2.4 to 9.5) in the 60 minutes after marijuana use. The elevated risk rapidly decreased thereafter. Conclusion: Smoking marijuana is a rare trigger of acute myocardial infarction.
Mittleman MA, Lewis RA, Maclure M, Sherwood JB, Muller JE. Triggering Myocardial Infarction by Marijuana. Circulation 2001;103(23):2805-2809.
Lindesmith Center (USA)
An analysis of the research methods used [in the study of Mittleman and colleagues] reveals glaring flaws. The sample size is statistically insignificant, no casual relationship has been established, and the study itself has never been replicated. (...) Out of 3,882 patients who had heart attacks, 124 were current marijuana smokers and 9 had smoked within an hour of their heart attack. Based on this minuscule, self-selected sample, Dr. Mittleman concludes that the risk of a heart attack is 4.8 times higher after smoking marijuana. The sample size alone renders the results meaningless. Assuming that Dr. Mittleman's conclusions are correct, the fact that heart attack risk for an otherwise healthy 50-year-old man is about 10 in 1 million highlights the sensationalism of the widespread publicity the study is receiving.
Lindesmith Newsletter. Junk Science Makes Headlines. Questionable Study Links Marijuana Smoking and Heart Attacks. June 15, 2001.
L.A. Gottschalk and colleagues
In view of associated findings that marijuana smoking decreased myocardial oxygen delivery, decreased exercise time until the onset of anginal pain, and increased myocardial oxygen demand in anginal patients, the use of marijuana by such patients is clearly inadvisable. Gottschalk LA, Aronow WS, Prakash R. Effect of marijuana and placebo-marijuana smoking on psychological state and on psychophysiological cardiovascular functioning in anginal patients.
Biol Psychiatry 1977;12(2):255-266.
The overall effect of cannabis use on the frequency of heart attacks is unknown. This can only be ascertained in longitidudinal epidemiological studies. There are some studies and case reports that support the assumption that cannabis use may be harmful in people with coronary disease and may trigger a heart attack. However, this seems to be a very rare event. Cannabis will not cause a heart attack in a healthy person.
There are some pharmacological effects of cannabis that may act preventive and some that may be damaging.
Factors that may be damaging:
- The decrease of oxygen delivery to the heart (only if cannabis is smoked), due to the production of carbon monoxide.
- The increase of heart rate of about 45% on average in the first hour after smoking. Thus a normal heart rate of 70 may increase to about 100. This increases labour and thus oxygen demand (or oxygen need) of the heart muscle.
- Changes of blood pressure. Cannabis may cause the blood pressure to increase when the person is lying down, and to decrease when the person stands up.
Factors that might be preventive:
- If the angina is based on a spastic contraction of the coronary arteries, cannabis may relax the spasm.
- Cannabinoids reduce platelet aggregation, thus they may reduce the tendency of the blood to form clots.
- Cannabinoids act anti-inflammatory. Inflammation measured as the level of CRP is associated with a higher risk of heart attack.
In coronary disease the heart attack risk of cannabis use may be as high as going for a walk or having sex. So if you feel chest pain while walking or if you know that you have a severe coronary disease you should better not take cannabis or only in low doses that do not significantly increase heart rate. These low doses are often high enough for the therapeutic effectiveness of cannabis. You can measure your heart rate yourself and find out how it changes in reaction to cannabis. In case of an accidential overdose you can prevent the increase of heart rate by taking a beta-blocker.
Chromosomal damage: Does cannabis cause damage to the genes?
House of Lords
There is no evidence that cannabis adversely affects human fertility, or that it causes chromosomal or genetic damage.
House of Lords Select Committee on Science and Technology. Cannabis. The scientific and medical evidence. London: The Stationary Office, 1998.
World Health Organization
There is general consensus that both cannabis and certain constituents of cannabis preparations (or in some cases cannabis smoke condensates) may indeed have mutagenic effects in the Ames assay for mutagenicity. On the other hand, pure THC as such has been found to have no mutagenic effects.
World Health Organization. Cannabis: a health perspective and research agenda. Genf: Division of Mental Health and Substance Abuse, WHO, 1997.
Cannabis smoke can exert mutagenic activity as a result of carcinogens (benzpyrenes, nitrosamines). This was established in the Ames test. THC itself is not mutagenic. THC may reduce the synthesis of DNA, RNA and proteins and modulate the normal cell cycle. To obtain those effects, however, very high doses were required in cell studies.
Nova-Institute. Hemp foods and THC levels: A scientific assessment. Sebastopol, USA: Hemptech, 1998.
(The Ames Assay is a test that combines several strains of bacteria to screen medical devices or compounds for mutagenic activity.)
Male fertility: Do cannabis or THC have a negative influence on sex hormones and sperms?
Wayne Hall, Nadia Solowij & Jim Lemon
High doses of THC probably disturb the male and female reproductive systems in animals. They reduce secretion of testosterone, and hence reducing sperm production, motility, and viability in males. It is uncertain whether these effects also occur in humans. Studies in humans have produced both positive and negative evidence of an effect of cannabinoids on testosterone, for reasons that are not well understood. Hollister has argued that the reductions in testosterone and sperm production observed in the positive studies are probably of "little consequence in adults", although he conceded that they could be of "major importance in the prepubertal male who may use cannabis." The possible effects of cannabis use on testosterone and spermatogenesis may be most relevant to males whose fertility is already impaired for other reasons, e.g. a low sperm count.
(Please note: This text has been taken from a scientific article. Some sentences have been changed to improve understandability.)
Hall W, Solowij N, Lemon J. The Health and Psychological Consequences of Cannabis Use. National Drug Strategy Monograph Series No. 25. Canberra: Australian Government Publishing Service, 1994.
In human males, cannabis smoking has been shown to decrease blood levels of the three hormones LH, FSH, and testosterone. Moreover, an increased incidence of low sperm count has been reported in men who were heavy marijuana smokers. Other studies did not find measurable differences in men who were light or heavy marijuana users. Acute THC treatment produces a consistent and significant dose- and time-related decrease in LH and testosterone levels in male rodents. In the male rhesus monkey, an acute dose of THC produced a 65% reduction in blood testosterone levels by 60 min of treatment that lasted for approximately 24 hr.
(Please note: This text has been taken from a scientific text. Some sentences have been changed to improve understandability.)
Murphy L. Hormonal system and reproduction. In: Grotenhermen F, Russo E, eds. Grotenhermen, F., Russo, E. (eds.): Cannabis and cannabinoids. Pharmacology, toxicology, and therapeutic potential. Haworth Press, Binghamton/New York 2001, in press.
Lynn Zimmer & John Morgan
By giving large doses of THC to animals, researchers have produced appreciable effects on sex hormone levels. However, the effects vary from one study to another, depending on the dose and timing of administration. When effects occur, they are temporary. (...) In neither male nor female animals have researchers produced permanent harm to reproductive function from either acute or chronic marijuana administration. (...) There is no convincing evidence of infertility related to marijuana consumption in humans. There are no epidemiological studies showing that men who use marijuana have higher rates of infertility than men who do not. Nor is there evidence of diminished reproductive capacity among men in countries where marijuana use is common. It is possible that marijuana could cause infertility in men who already have low sperm counts, However, it is likely that regular marijuana users develop tolerance to marijuana's hormonal effects. (...) Marijuana has neither a masculinizing effect in females nor a feminizing effects in males.
Zimmer L, Morgan JP. Marijuana Myths Marijuana Facts. A review of the scientific evidence. New York/San Francisco: The Lindesmith Center, 1997.
House of Lords
Animal experiments have shown that cannabinoids cause alterations in both male and female sexual hormones; but there is no evidence that cannabis adversely affects human fertility, or that it causes chromosomal or genetic damage.
House of Lords Select Committee on Science and Technology. Cannabis. The scientific and medical evidence. London: The Stationery Office, 1998.
Asthma: How should cannabis or THC be taken to treat asthma?
British Medical Association
Acute doses of cannabis and THC exert a definitive bronchodilator effect on the small airways of the lungs. The mechanism of this effect is not known, but it appears to be different from that of other drugs used at present as bronchodilators for asthma. (…) However, there have been very few studies on the bronchodilator effects of cannabinoids in asthmatic patients. All of these were studies carried out in the 1970s. Tashkin et al. studied 14 asthmatic volunteers and compared smoked cannabis (2%THC), oral THC (15mg) and the drug isoprenaline (0.5%). They found that smoked cannabis and oral THC produced significant bronchodilatation of at least two hours duration. The effect of smoked cannabis was nearly equivalent to the clinical dose of isoprenaline. Smoked cannabis was also capable of reversing experimentally induced bronchospasm in three asthmatic subjects. (…) Williams et al. compared a THC aerosol containing 0.2 mg THC with a salbutamol aerosol (0.1 mg) in 10 asthmatic subjects. Both drugs significantly improved respiratory function. The onset of effect was more rapid with salbutamol, but the effects of both drugs were equivalent at one hour. Tashkin et al. compared several doses of THC aerosol (5-20mg) with a standard dose of isoprenaline in 11 normal volunteers and five asthmatic subjects. In the normal subjects and three of the asthmatics, the bronchodilator effect of THC was less than that of isoprenaline after five minutes, but significantly greater after one to three hours.
(Please note: This text has been taken from a scientific article. Some sentences have been changed to improve understandability.)
British Medical Association: Therapeutic Uses of Cannabis. Amsterdam: Harwood Academic Publishers, 1997
The treatment of asthma includes the use of anti-inflammatory drugs (corticosteroids) and bronchodilators. THC and cannabis are bronchodilators and may also exert some anti-inflammatory and anti-allergic action. Cannabis smoke contains combustion products qualitatively similar to those found in tobacco smoke, among them several carcinogens that may damage the mucosa. The inhalation of these combustion products should be avoided or strongly decreased. To avoid the intake of combustion products cannabis can be taken orally. To decrease the amount of inhaled carcinogens cannabis or THC can be inhaled by a vaporizer, and/or cannabis with a high THC content can be used/smoked. In several situations, a combination of a basic oral medication and a demand inhaled medication in acute asthma attacks may be useful to reduce the risks from smoking and the risk of overdosage with oral administration. The availability of a THC aerosol is desirable.
Calignano and colleagues
An international research group has discovered why marijuana causes coughing in some situations but may inhibit bronchospasm and cough in others. This finding could lead to better treatments of respiratory diseases. In a report in the journal Nature scientists from the Institute of Experimental Medicine in Budapest (Hungary), the University of Naples (Italy) and the University of Washington (USA) showed how the endocannabinoid anandamide influences the airways in the lungs. In animal studies with guinea pigs and rats, anandamide exerted a dual effect on bronchial responsiveness. If the muscles in the lungs were constricted by an irritant (capsaicin) the endocannabinoid relaxed the smooth muscles and strongly inhibited coughing. But if the airways were relaxed (by removing the constricting effect of the vagus nerve) anandamide caused a coughing spasm. Anandamide is synthesized in lung tissues and its effects are mediated by cannabinoid receptors. (…)
IACM-Bulletin of 12 November 2000; Calignano A, et al: Bidirectional control by airway responsiveness by endogenous cannabinoids. Nature 2000;408:96-101.
Interaction: Does cannabis/THC interact with other drugs used for the treatment of diseases?
Although medical marijuana is not officially approved, marijuana has been tried empirically for treating a variety of medical disorders, such as nausea and vomiting associated with cancer chemotherapy, weight loss associated with AIDS, and spasticity from neurological diseases. In each instance, other drugs are also present. So far, no adverse interactions from such use have been reported. However, this might not reflect the true frequency. Unless one looks for something, one is not likely to find it. (...) The published literature, at least in regard to studies with humans, has been rather silent. Usually this silence indicates that no meaningful interactions have been observed in the real life use of marijuana as compared with experimental studies. (...) One of the most reasonable therapeutic uses of marijuana and THC has been to ameliorate the nausea and vomiting associated with cancer chemotherapy. Thus, cannabinoids will be used simultaneously with many highly toxic cancer drugs. (…) In none of the reports of use of THC or marihuana in patients simultaneously undergoing cancer chemotherapy has there been any mention of increased toxicity of anticancer drugs. Nonetheless, the absence of such reports may signify that no attempt was made to look for them. This avenue of research should be encouraged. A somewhat similar situation applies to the therapeutic use of orally administered THC in treating the weight loss associated with AIDS. (…) THC or marihuana has been used for treating spasticity associated with neurological disorders, such as multiple sclerosis and spinal cord injury. Since THC may be added to therapies with muscle relaxants, it would be of some interest to know whether such combined uses might be harmful. In one animal study in which THC was given with muscle relaxants, it was found to increase the desired effect of the latter drugs. In this case, the interaction might be advantageous.
(Please note: This text has been taken from a scientific article. Some sentences have been changed to improve understandability.)"
Modified according to: Hollister LE. Interactions of marihuana and D9-THC with other drugs. In: Nahas G, Sutin KM, Harvey DJ, Agurell S, eds. Marihuana and medicine. Totowa, NJ: Humana Press, 1999, pp. 273-277.
Cannabis and dronabinol (THC) have been used in combination with a multitude of medications without significant deleterious drug interactions. Clinical studies in the beginning of the 20th century often demonstrated mutual enhancement of therapeutic effects of cannabis preparations and other drugs. In modern therapeutic concepts a combination of cannabis/THC with other medications could also be of benefit for many indications. Cannabis has been used illegally by individuals suffering from many diseases concomitantly with numerous prescription medicines. No unwanted side effects of clinical relevance have been observed to date. (…) Other medicines may enhance or attenuate certain actions of cannabis/THC or certain actions of these medicines may be enhanced or attenuated by cannabis/THC. Moreover, it is possible that certain effects are enhanced and others reduced, as is the case with phenothiazines applied against side effects of cancer chemotherapy (see below). Of greatest clinical relevance is reinforcement of the sedating effect of other psychotropic substances (alcohol, benzodiazepines), and the interaction with substances that act on the heart (amphetamines, adrenaline, atropine, beta-blockers, diuretics, tricyclic antidepressants, etc.). (…)
- Anti-cholinergics: Atropine and scopolamine may increase the acceleration of heart frequency by THC.
- Anti-cholinesterases: Physostigmine antagonizes the psychotropic effects and the acceleration of heart frequency produced by THC. (…) · Anti-depressants (selective serotonin reuptake inhibitors): THC may increase the effect of fluoxetine.
- Anti-depressants (tricyclics): Frequency of the heart, blood pressure lowering and sedating effects of amitriptyline may be enhanced.
- Benzodiazepines: Respiratory depression and depression of the brain function may be increased. The antiepiletic action may be enhanced.
- Beta-blockers: They reduce increase of heart frequency associated with THC.
- · Glaucoma: Several drugs that decrease intraocular pressure and cannabinoids may act additively.
- Neuroleptics: THC may antagonize the antipsychotic actions of neuroleptics. It may improve their therapeutic effects in motor disorders.
- Non steroidal antiinflammatory drugs (NSAID): Indomethacin, acetylsalicylic acid (aspirin), and other NSAIDs antagonize THC effects. Indomethacin significantly reduced subjective "high" and acceleration of heart frequency.
- Opiates: Enhancement of sedation and pain reduction.
- Phenothiazines: Prochlorperazine and other phenothiazines attenuate the psychotropic effects of THC and increase its antiemetic effects.
- Sympathomimetics: Amphetamines and other sympathomimetics enhance the acceleration of heart frequency and the increase of blood pressure.
- Theophylline: The metabolism of theophylline is accelerated by THC. Thus, higher doses of theophylline might be necessary.
(Please note: This text has been taken from a scientific article. Some sentences have been changed to improve understandability.)
Grotenhermen F. Practical hints. In: Grotenhermen F, Russo E, eds. Cannabis and cannabinoids. Pharmacology, toxicology, and therapeutic potential. Haworth Press, Binghamton/New York 2001, in press.
Pregnancy: Does cannabis/THC do harm to the fetus if it is used during pregnancy?
Institute of Medicine
Among the studies that have investigated the relationship between prenatal marijuana exposure and birth outcome, the results have been inconsistent. Except for adolescent mothers, there is little evidence that gestation is shorter in mothers who smoke marijuana. Several studies of women who smoked marijuana regularly during pregnancy show that they tend to give birth to lower weight babies. (...)
For most of these studies, much of the harms associated with marijuana use are consistent with those associated with tobacco use, and smoking is a significant factor so the contribution of cannabinoids cannot be confirmed. However, Jamaican women who use marijuana rarely smoke it, but instead prepare it as tea. In a study of neonates born to Jamaican women who either did or did not ingest marijuana during pregnancy, there was no difference in neurobehavioral assessments made at 3 days after birth and at one month. (...)
Since 1978, the Ottawa Prenatal Prospective Study has been measuring the cognitive functions of children born to mothers who smoked marijuana during pregnancy. (...) The children in the different marijuana exposure groups showed no lasting differences in global measures of intelligence such as language development, reading scores, and visual or perceptual tests. Moderate cognitive deficits were detectable among these children when they were four days old and again at four years, but these deficits were no longer apparent at five years. Prenatal marijuana exposure was not, however, without lasting impact. By comparison, at both ages 5-6 and 9-12, children in the same study who were prenatally exposed to tobacco smoke scored significantly lower on tests of language skills and cognitive functioning.
Joy JE, Watson SJ, Benson JA, eds. Marijuana and medicine: Assessing the science base. Institute of Medicine. Washington DC: National Academy Press, 1999.