CANADIAN CONSORTIUM FOR THE INVESTIGATION OF CANNABINOIDS IN HUMAN THERAPEUTICS (CCIC)
Submission to The Senate Committee on Illegal Drugs
June 11, 2001
Contact Information:
Mary Lynch, MD, FRCPC
Director CCIC
Director of Research
Queen Elizabeth II Health Sciences Centre
4th Floor Dickson Centre
5820 University Avenue
Halifax, Nova Scotia, B3H 1V7
1. THE IMPORTANCE OF CANNABINOID RESEARCH
1. Introduction
2. Distribution of Cannabinoid Receptors
3. Endogenous Cannabinoid System
4. Mechanism of Action
5. Cannabinoids and Pain
5.1 Preclinical Work
5.2 Clinical Implications and Human Wor
6. Cannabinoids and Anti-inflammatory Action
7. Cannabinoids in the Treatment Nausea and Vomiting and Wasting Syndrome in HIV Infected Patients
8. Cannabinoids in the Treatment of Spasticity
9. Cannabinoids in Glaucoma
10. Beyond Marijuana
11. Cannabinoids and the Immune System
12. Summary
2. CANNABINOID RESEARCH AN INTERNATIONAL PERSPECTIVE
1. National Reviews of Cannabis as Medicine
2. Potential Medical use of Pure Cannabinoids
3. Views on Medical use of Smoked Cannabis (Marijuana)
3. MISSION STATEMENT, AIMS AND OBJECTIVES OF THE CCIC
4. THE CHALLENGE OF PURSUING CANNABINOID RESEARCH IN THE CURRENT SOCIOPOLITICAL CLIMATE
1. THE IMPORTANCE OF CANNABINOID RESEARCH
Cannabinoids are compounds that exhibit a pharmacological profile similar to D -9 tetrahydrocannabinol (D -9-THC), the main psychoactive principle found in herbal cannabis or marijuana. Herbal cannabis has been used for centuries for medicinal purposes (reviewed Mechoulam 1986) but it has only been in the last 40 years that scientists have been able to elucidate the molecular basis of cannabinoid action.
Modern pharmacology of cannabinoids began in 1964 when the major psychoactive constituent of cannabis, D -9-THC, was synthesized in pure form and its structure elucidated (Gaoni and Mechoulam 1964). Following this discovery scientists were able to begin synthesizing this group of chemicals and over the following two decades many papers were published regarding the chemistry, pharmacology, metabolism and clinical actions of cannabinoids. However the mechanism of action remained a mystery until the 1980’s (reviewed Mechoulam 2001).
The first crucial step in elucidating how cannabinoids work in the body was achieved in 1988. At that time a radiolabeled potent synthetic cannabinoid was found to bind to brain membranes in a highly specific and selective manner, exhibiting features suggesting that these chemicals were attaching to specific receptors (Devane 1988). Within a short time the cannabinoid receptor (now called CB1) was discovered and cloned from rat and human brain (Matsuda 1990). Three years later a peripheral cannabinoid receptor (CB2) was discovered and cloned (Munro 1993). Since then researchers around the world have mapped the location of CB1 and CB2 receptors in the body as well as identified the ways in which they work.
2 Distribution of Cannabinoid Receptors
The distribution of cannabinoid receptors in the nervous system has been examined by several methods (Herkenham 1991, Mailleux 1992, Tsou 1998). It is now known that high levels of CB1 receptors are located in areas important for memory and coordination (hippocampus, basal ganglia, cerebellum ), higher cognitive functioning (cerebral cortex) and the reward centre (nucleus accumbens). Moderately abundant concentrations are located in areas important in the transmission and modulation of pain all the way from the brain to the sensory nerves (periaqueductal gray of the midbrain, rostral ventrolateral medulla, superficial layers of the spinal dorsal horn and dorsal root ganglion and peripheral sensory nerves). In addition, CB1 receptors are located in areas controlling temperature regulation and endocrine and reproductive function (hypothalamus and pituitary), emotional responses and fear (amygdala), arousal (brainstem) and nausea and vomiting (nucleus of the solitary tract) (Herkenham 1991, 1995; Hohmann 1998, 1999a 1999b; Pertwee 1997; Sanudo-Pena 1999, Wenger 1999). There are low levels of CB1 receptors in brainstem centers that control breathing and blood circulation which probably accounts for the high safety margin of the cannabinoids (Walker, 2001). The identification of receptors in all of these areas is consistent with the behavioral and physiological effects produced by cannabinoids.
The first CB2 receptors were cloned not from brain, but from a human immune cell line (Munro 1993), thus it was apparent from the beginning that the cannabinoid system extended beyond the nervous system. Since that time studies have demonstrated the presence of CB2 receptors throughout the immune system (reviewed by Klein 1999, 2001).
This work has established the current model for cannabinoid receptors with CB1 primarily located in brain and associated structures such as pituitary and peripheral nervous tissues, while CB2 is primarily located in the peripheral reproductive and immune systems (Klein 2001).
3. Endogenous Cannabinoid System
When a receptor for a particular substance is identified but that substance does not normally exist in the body, the logical question to ask is, "Why does the receptor exist?" The existence of a receptor in the body suggests that there is probably an endogenous substance or in this case a marijuana-like chemical, that is naturally produced and which acts at the receptor. Two endocannabinoids have been identified. The first was N-arachidonylethanolamine (anandamide) (Devane 1992) the second was N-arachidonylglycerol (Mechoulam 1995, Sugiura 1995).
We now know that the body is able to produce marijuana like chemicals which can act in a system of receptors that extends throughout the nervous and immune systems. The next step was to further elaborate the mechanism of action and identify the natural function of these compounds.
There is a large body of research which has identified how the cannabinoids work (reviewed in Joy 1999, Mechoulam 2001). The overall effect is that of cellular inhibition. This is very much like the mechanism of action of the opioids (pain relief medications such as morphine). The cannabinoids and opioids have similar actions but can act independently. For example, the CB1 receptor antagonist SR141716A (antagonists are molecules that can bind to the receptor without activating the cell) prevents the analgesic effects of THC but not of morphine (Lichtman 1997) whereas naloxone, an opioid antagonist blocks the analgesic effect of morphine but not of THC and its analogs (Howlett 1995). Of interest is the fact that CB1 receptors are ten times more abundant than mu opioid receptors in the brain (Sim 1996).
Thus cannabinoids exhibit a mechanism of action very much like the action of the morphine group of drugs but are able to act independently. The cannabinoid system is larger and occupies more areas than the opioid system, with the implication that the cannabinoid system may have wider potential therapeutic applications.
Pre-clinical work reveals that cannabinoids block pain responses in virtually every pain model tested. One of the earliest studies was done by Walter Dixon (1899), who demonstrated that cannabis was able to suppress canine reactions to pinprick. In models of acute or physiological pain cannabinoids are highly effective against thermal, mechanical, and chemical pain and are comparable to opioids in potency and efficacy (Walker 2001).
In models of chronic pain cannabinoids exhibit even greater potency and efficacy in both inflammatory (Tsou 1995) and neuropathic pain (pain due to nerve damage) (Herzberg 1997). Because cannabinoids are able to affect motor systems as well it is important to establish that the slowed reactions of animals in pain tests are not because of slowed motor activity rather than pain inhibition. In this case it is helpful to examine the results of electrophysiological studies where extracellular single neuron recordings are obtained from anesthetized rats. In this case the responses of both nociceptive (pain related) and non-nociceptive (non-pain related) neurons can be studied. In a review of these studies (Walker 2001) it has been concluded that cannabinoids produce profound suppression of cellular nociceptive responses with no suppression of the low threshold mechanoreceptive neurons (respond to touch only). These experiments included suppression of neurophysiological responses to all types of nociceptive stimuli tested, suppression of windup (a model of central sensitization observed in chronic pain) and suppression of increased spontaneous firing following injection of the inflammatory agent complete Freunds adjuvant (Hohmann 1995, 1998, 1999 a&b; Martin 1996; Strangman 1999; reviewed in Walker 2001). Thus cannabinoids exhibit analgesic efficacy in animal models of acute and chronic pain. In other words cannabinoids are good pain killers.
It has also been demonstrated that cannabinoids act at multiple levels in the modulation of nociceptive or pain-related transmission (reviewed in Walker 2001). Injection of cannabinoids directly into the central chambers of the brain (Martin 1993) supressed tail-flick responses and spinal nociceptive responses (Hohmann 1999a). Direct brain injections into areas involved in descending inhibition of spinal nociceptive neurons elicits antinociceptive effects (decreases the neural activity related to noxious stimuli), these areas include the PAG in the midbrain, the rostral ventrolateral medulla (RVM), and the nordrenergic nucleus A5 in the medulla (Martin 1995,1998,1999). Through a series of experiments involving animal behavior (tail flick) and extracellular single unit recordings from RVM neurons along with administration of specific cannabinoid and opioid agonists and antagonists it has been demonstrated that cannabinoids produce analgesia through the same brainstem circuit used for opioid analgesia. The use of an opioid is not required for the cannabinoids to produce this effect (Meng 1998).
Further work has demonstrated that endocannabinoids participate in endogenous pain modulation by actions in the PAG. Administration of cannabinoid antagonists produces hyperalgesia (increased response to painful stimuli) and blocks the analgesia produced by electrical stimulation of the dorsal PAG (Richardson 1997, Strangman 1998). The pro-nociceptive (pain producing) actions of the antagonist are reasonable evidence for an anti-nociceptive action of one or more of the endo-cannabinoids. To examine the role of endocannabinoids further Walker (1999) used microdialysis in the PAG. This method permits the collection of neurotransmitters from the extra-cellular space and is an indicator of release of these modulators. Using liquid chromatography/mass spectrometry it was established that the analgesia produced by electrical stimulation or by injection of the chemical irritant formalin into the hindpaws of anesthetized rats, was associated with the release of anandamide in the PAG. Thus it appears that either pain itself, or electrical stimulation leads to release of anandamide, which then acts on cannabinoid receptors in the PAG to inhibit nociception.
Several investigators have demonstrated that cannabinoids also inhibit pain by a direct spinal action (Yaksh 1981, Welch 1992, Lichtman 1991 a&b, Hohmann 1998; Richardson 1997, 1998 a&b). These observations are consistent with the labeling studies exhibiting the presence of cannabinoid receptors in the dorsal horn of the spinal cord.
Cannabinoids also act in the periphery. Injections of low doses of anandamide leads to a reduction in the hyperalgesia caused by carageenan, a chemical which induces an inflammatory reaction in the paw (Richardson 1998c). This is consistent with work reviewed above which has identified the presence of cannabinoid receptors in the peripheral nerve.
In summary the evidence supports that cannabinoids are analgesic, that an endo-cannabinoid system is a part of the body’s pain defense network, and that the analgesic effect occurs at multiple levels from the brain to the peripheral nerve.
5.2 Clinical Implications and Human Work
Considering the fact that animal research has demonstrated clearly that cannabinoids are analgesic and that there is an endogenous cannabinoid system in the body which modulates pain transmission it is surprising that there are so few randomized controlled trials examining the analgesic action of this group of chemicals in human pain.
To date there are six controlled studies examining cannabinoid effects in human pain. In experimental pain smoked cannabis was found to increase sensitivity to electrically induced pain in 26 men (Hill 1974). In a study of ten patients with post extraction dental pain intravenous THC was found to be inferior to placebo and diazepam. This study only measured extremes of pain tolerance rather than pain intensity (Gregg 1976). In a third study intravenous THC was effective in reducing surgical pain (Raft 1977).
There are three randomized controlled trials examining cannabinoids in chronic pain. In cancer pain oral D -9-THC has been found to exhibit an analgesic effect roughly equivalent to codeine but sedation was a significant side effect (Noyes 1975 a&b). In an N-of-1 trial oral THC reduced the pain of familial Mediterranean fever (Holdcroft 1997).
6 Cannabinoids and Anti-inflammatory Action
In addition to direct analgesic effects there is evidence that cannabinoids are anti-inflammatory. Cannabinoids act on CB2 receptors located on mast cells (cells involved in the body’s infection and injury defense system) to directly attenuate the release of inflammatory agents such as histamine and serotonin (Facci 1995). Palmitoylethanolamide (PEA), a CB2 agonist attenuates carageenan-induced mechanical hyperalgesia and edema by down-modulating mast cell formation after injury (Mazzari 1996). The dimethylheptyl derivative of THC-11 oic acid, a non-psychoactive derivative, supresses acute and chronic inflammatory changes in mice when given orally (Zurier 1998). Another non-psychoactive cannabinoid, HU-211, has been shown to supress inflammation that is caused by mobilization of cytokines such as TNFa (Bass 1996 , Shohami 1997). Thus there is evidence that cannabinoids can exert a number of anti-inflammatory effects with significant potential applications in the treatment of arthritis.
7. Cannabinoids in the Treatment of Nausea and Vomiting and Wasting Syndrome in HIV Infected Patients
Chemotherapy induced nausea and vomiting and AIDS related anorexia associated with weight loss are the only currently approved indications for the use of oral cannabinoids available in Canada (Marinol/dronabinol/D -9-THC, Cesamet/nabilone).
Nausea and vomiting are produced by excitation of one or a number of triggers in the gastrointestinal tract, brainstem and higher brain centers. There are numerous cannabinoid receptors in the nucleus of the solitary tract, a brain center important in control of emesis (vomiting) (Herkenham, 1995). Several cannabinoids have been tested as antiemetics, including THC (both D -9-THC and D -8-THC) and the synthetic cannabinoids nabilone and levonantrodol. Smoked marijuana has also been examined (reviewed in Joy 1999).
Most of the research has been done on THC and analogues (reviewed in Joy 1999). It has been concluded that cannabinoids are modest anti-emetics (anti-vomiting agents). There are more effective anti-emetic agents available, however antiemetics work through several mechanisms and cannabinoids may provide an additional option for treatment of nausea and vomiting that has not responded to other agents (Joy 1999). A Canadian oncology group has conducted a double-blind crossover placebo-controlled trial comparing smoked marijuana with oral THC. They examined the anti-emetic effects in a group of 20 patients who were receiving various chemotherapeutic drugs and found the degree of emetic control was similar. Twenty five percent of patients received complete control of emesis, 35% indicated a slight preference of the pill over the marijuana and 20% preferred marijuana, 45% expressed no preference (Levitt 1984).
Although marijuana has received significant attention in the press for treatment of malnutrition and wasting in HIV infected patients in addition to numerous anecdotal accounts claiming benefits, there is very little published work about the effectiveness of marijuana or cannabinoids for the treatment of malnutrition or wasting syndrome in HIV-infected patients. The only cannabinoid evaluated in controlled trials is D -9-THC (dronabinol). It has been demonstrated that short term (six week) and long term (one year) therapy with dronabinol is associated with an increase in appetite and stable weight. In a small trial of five patients over five weeks dronabinol was shown to increase body fat by 1% (Beal 1995,1997; Strue 1993). Megestrol acetate, a synthetic derivative of progesterone has been found to be more effective than dronabinol in stimulating weight gain and other treatments such as anabolic compounds including testosterone and growth hormone are under investigation (reviewed by Joy 1999). Enteral and parenteral nutrition have also been evaluated and found to increase weight but the gain is due more to body fat than muscle and other lean tissues (Kotler 1990,1991).
In summary cannabinoids may provide an additional treatment option in the management of nausea, vomiting and wasting in patients with cancer who require chemotherapy and in HIV infected individuals but further research is needed in order to identify the best and most specific agents and additional options for drug administration.
8 Cannabinoids in the Treatment of Spasticity
Marijuana or THC is reported to have an antispasticity effect in patients with multiple sclerosis (MS) and spinal cord injury according to anonymous questionnaire and case reports (Malec 1982, Meinck 1989, Consroe 1998, NIH report ). In addition several controlled studies with objective measures of spasticity as well as subjective self-reports have shown improvement after oral and rectal administration of THC or nabilone (Petro 1981, Ungerleider 1987, Martyn 1995, Brenneisen 1996, reviewed by Kalant 2001). To date, there have been no controlled studies comparing the antispasticity effects of smoked marijuana and oral THC in the same patients, and no controlled comparisons with other drugs currently used for the relief of spasm.
There is significant evidence that cannabinoids administered orally, intravenously and by inhalation can decrease intraocular pressure (IOP) by 25% in healthy volunteers and patients with glaucoma (reviewed Joy 1999). Present treatment for glaucoma is focused on the decrease of IOP which is one of the major risk factors involved in the degeneration of the optic nerve leading to blindness in individuals suffering from glaucoma. Currently there are several classes of drugs as well as surgical options available. The short duration of action on IOP (3-4 hours) and unpleasant side effects decrease the probability that THC or marijuana will be reasonable alternatives to current agents in treating glaucoma. The next generation of treatment for glaucoma will target neural protection, rescue and regeneration. As mentioned above there are already newer synthetic cannabinoids that have exhibited neuroprotective effects, thus there is potential for cannabinoid development in the treatment of glaucoma. The development of non-irritating, water soluble derivatives of THC, that could be used as eyedrops, also offers possibilities for future use of cannabinoids in glaucoma (Kalant 2001).
The debate surrounding medical marijuana involves two key questions: Should we permit smoking of medications and does the crude plant material have some effects that differ from the currently available oral synthetic D -9-THC.
Oral preparations of THC are currently available in Canada. Why not use the oral cannabinoids on the market? In some cases this may be reasonable but in many cases the utility of these agents (Marinol, Cesamet) is hindered by their slow and unpredictable absorption. This is a drawback and these agents produce dysphoria at higher doses, it is this side effect that is the main limiting factor in dosing in humans (Walker,2001).
Laboratories around the world are working on the identification of compounds which retain the therapeutic effects but do not have the unwanted side effects of D -9-THC and are better absorbed following oral administration. Another emphasis is the development of alternate delivery systems for these drugs so that delivery into the body is efficient but smoking is not necessary.
One example of these new compounds is found in the experimental compound ajulemic acid (1’,1’dimethylheptyl-D 8-THC-11-oic acid,CT-3).This compound, which is under development by Atlantic Pharmaceuticals, produces analgesia, but is almost entirely lacking in side effects in animals (Burstein 1998). Another compound, HU-211, also called Dexanabinol, is a non-psychotropic enantiomer (mirror-image) of one of the most potent synthetic cannabinoids prepared to date (HU-210). Dexanabinol has been found to block the uptake of radioactive calcium and protect neurons from glutamate neurotoxicity mediated by NMDA receptors and displaces NMDA from its glutamate binding site. It is a scavenger of peroxy radicals which cause oxidative damage to cells and strongly inhibits the release of TNF-a (reviewed in Mechoulam 2001). This combination of effects suggests that dexanabinol shows promise in limiting nerve injury. Pre-clinical trials in animal models of brain injury demonstrated HU-211 was effective in improving cognitive and motor function. Investigators are now proceeding with trials in humans. In Phase II trials examining 67 patients with severe head trauma in six major hospitals in Israel, increases in intracranial pressures were attenuated by this compound and there was a consistent trend towards better overall outcome as determined by the Glasgow Coma outcome scale (reviewed Mechoulam 2001).
Another direction worthy of research is to develop chemicals that will enhance the activity of endocannabinoids. It may be possible to develop new drugs that enhance synthesis, block re-uptake or inhibit breakdown of the endocannabinoids similar to the way the monoaminergic system is manipulated in the treatment of depression.
The research directions described above are exciting but will take time, in the meantime we need further research regarding currently available cannabinoids including herbal cannabis in smoked and oral forms.
Studies examining efficacy and safety of herbal cannabis in pain, spasticity, nausea and vomiting are needed.
11 Cannabinoids and the Immune System
Because cannabinoid receptors are found throughout the immune system there is potential to manipulate this system beyond the anti-inflammatory effects reviewed above. It is also important for researchers to be aware of potential immune effects in research examining other therapeutic indications. A number of excellent reviews have been published (Klein 1999, 2001 and reviewed in Joy 1999). This literature is too extensive to review here but Klein has summarized the current work in his most recent review:
"The immune system is extremely complex consisting of a variety of organs, cells, tissues, and soluble factors working together to produce a plethora of effector functions. This complexity provides many avenues for cannabinoids to alter immune function and over the last decade or so, many of these avenues have been examined. From a variety of experimental paradigms, cannabinoids have been shown repeatedly to modulate immune function. However, from these studies it cannot be concluded that marijuana smoking causes severe immunodeficiency in humans. What can be concluded is that these drugs have the potential to modulate immune function through both receptor and non-receptor mediated mechanisms. Clearly, additional studies are needed to determine: the precise structure and function of the putative immunocannabinoid system; the potential therapeutic usefulness of these drugs in chronic diseases such as AIDS and multiple sclerosis; the effects of these agents on tumor growth and induction of apoptosis; and the potential anti-inflammatory and proinflammatory properties of cannabimimetic compounds. It is likely that the cannabinoid system along with other neuroimmune systems has a subtle but significant role in the regulation of immunity and that this role can eventually be exploited in the management of human disease" (Klein, 2001)
In summary the current literature supports that there is a complete cannabinoid system in the body that regulates various physiological processes in both brain and peripheral tissues and there is significant potential to manipulate this system in treating human suffering and disease. Further research regarding the role of cannabinoids in the treatment of a variety of health conditions is needed and should be facilitated.
2. CANNABINOID RESEARCH AN INTERNATIONAL PERSPECTIVE
1. National Reviews of Cannabis as Medicine
In the past seven years, national medical and scientific groups in the U.K., the U.S.A., the Netherlands and Australia, as well as an Expert Review Panel of the World Health Organization (WHO), have reviewed in depth the question of potential therapeutic use of cannabis and cannabinoids.
These reviews have led to reports from the Australian National Drug Strategy (Hall 1994), the Netherlands Health Council (Gezondheidsraad 1996), the British Medical Association (1997), the American Medical Association (1997), a House of Lords (UK) Select Committee (1998), the Royal Pharmaceutical Association in the UK (1999), the US National Academy of Sciences Institute of Medicine (Joy 1999), and the WHO (Hartel 1999). As may be expected from so many different reports, there are differences among their conclusions, but there is a striking measure of agreement about the major points.
2 Potential Medical use of Pure Cannabinoids
There is virtually unanimous agreement that pure cannabinoids, including not only THC but also synthetic derivatives and related compounds, will probably prove to be therapeutically useful in the relief of pain, muscle spasticity, nausea and vomiting, and severe weight loss (the wasting syndrome) in cancer and AIDS patients. There is some disagreement among these reports, about the potential value for the treatment of glaucoma, asthma, and epilepsy. All agree that more developmental research should be conducted with the goal of synthesizing a variety of cannabinoid derivatives that can be given by mouth, by injection, as eye drops, as suppositories, or inhaled from a nebulizer or a vaporizer. Such derivatives would broaden the range of potential medical uses, while avoiding some of the hazards of herbal cannabis.
3 Views on Medical use of Smoked Cannabis (Marijuana)
There is also virtually unanimous agreement that the smoking of crude cannabis is not a method that can be recommended for medical administration. This is because there is good evidence that cannabis smoke, like tobacco smoke, causes chronic inflammation of the airways, and some evidence that cannabis smoke also is a risk factor for cancer of the upper airways. Many of the diseases for which cannabinoids may prove to be useful are chronic diseases, which would require long-term or life-long administration of the drug. In such cases, the risk of cancer or other lung diseases would seriously limit the acceptability of smoking as a means of administering cannabis.
However, smoking does result in a rapid onset of action of the cannabinoids, and does offer, at least in theory, the possibility of "titrating" the dose, i.e., limiting the amount of drug inhaled to the minimum amount needed to relieve the symptoms. Therefore most (but not all) of these reports have recommended that short-term use of smoked cannabis might be tried for self-limited illnesses, or in patients with very short life expectancies, for whom the risk of long-term adverse effects of smoked cannabis is irrelevant. The Australian report discussed only the use of pure cannabinoids for medical purposes, but only the Netherlands Health Council report rejected out of hand any medical use of smoked cannabis.
A final consideration concerning tests of smoking is that there is still a need for scientific comparison of the effectiveness, tolerability, appropriate dosage, and hazards of smoked cannabis versus pure cannabinoids by mouth and other routes of administration. Such information can only be gained from well-designed clinical trials.
3. THE CCIC, MISSION STATEMENT, AIMS AND OBJECTIVES
The CCIC is a national interdisciplinary research consortium that came together in the Spring of 2000 as a result of initial funding from the CIHR. To date the CCIC has held four meetings clarifying priorities for cannabinoid research in Canada. The CCIC will facilitate both basic science and clinical trials examining cannabinoids as therapeutic agents. The CCIC is currently developing a national clinical trials network.
The CCIC’s mission is to bring together key Canadian researchers who will pursue excellence in basic science and clinical research on the cannabinoid system. The CCIC will liaise with members of Health Canada, CIHR and other bodies in order to facilitate cannabinoid research across the country.
The aims and objectives of the CCIC are to enhance the health of Canadians by using Canada’s strong research community to assess the role of cannabinoids in the treatment of a variety of health conditions.
4. THE CHALLENGE OF PURSUING CANNABINOID RESEARCH IN THE CURRENT SOCIOPOLITICAL CLIMATE
Because herbal cannabis (marijuana) is classified as an illegal substance research involving all cannabinoids is often delayed or obstructed. Acquisition of research materials (herbal cannabis and other cannabinoid preparations) is a problem. Further, researchers considering clinical trials using cannabis are burdened with additional licensing procedures for the acquisition, and distribution of study materials. Also there is the concern of protecting study subjects from prosecution under the criminal code for possession of an illegal substance. Our institutions, where this research is to be conducted, are uncomfortable and research protocols are often delayed in the ethics approval process due to concerns regarding the status of these substances.
This adds to the complexity of doing good research, given the differences among provinces and cities with respect to police practices concerning cannabis users.
1. Proceed with establishing policies or legislation that will facilitate the research climate regarding cannabinoids, legislation should accomplish:
- Protection of research subjects from prosecution under the criminal code in a way that preserves confidentiality and minimizes the need for additional documents.
- Directives to institutions and hospitals where this research is to take place that will facilitate the research review process.
- Assistance, guidance and a clear, straight forward and accountable process to researchers facilitating the acquisition of THC, synthetic cannabinoids and crude cannabis for research studies
2. Support epidemiological studies regarding the use of cannabis for therapeutic purposes in Canada.
3. Support Health Canada's initiative to study therapeutic cannabis use.
Recommend the clinical appraisal of the safety and efficacy of cannabis for therapeutic
purposes, and determine the short and long term health effects on therapeutic users
following existing drug development guidelines.
4. Support research into alternative delivery systems of cannabis preparations and cannabinoids.
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