Cannabis and cannabis resin

Technical information (most recent pre-review / critical review report)
ECDD Recommendation
Deleted from Schedule IV of the 1961 Single Convention on Narcotic Drugs
Recommendation (from TRS)

Substance identification
Cannabis is a flowering plant, generally dioecious (i.e. with the male and female flowers on separate plants). It has a characteristic odour, which is mainly attributable to a mixture of volatile compounds, including monoterpenes, sesquiterpenes and other terpenoid-like compounds.

Cannabis tops and cannabis resin (sometimes referred to as "hashish") are typically administered via inhalation after combustion (i.e. by smoking). Cannabis is defined in the 1961 United Nations Single Convention on Narcotic Drugs as the flowering or fruiting tops of the cannabis plant (excluding the seeds and leaves when not accompanied by the tops) from which the resin has not been extracted.

Cannabis resin is defined as the separated resin, whether crude or purified, obtained from the cannabis plant. The resinous secretions of the plant can be collected to yield a product with a higher concentration of Δ9-THC than occurs in the whole plant inflorescence. In addition to the secretions, cannabis resin consists of finer plant material and appears as a loose or pressed sticky powder, depending on the method of production.

WHO review history
Cannabis, cannabis resin, extracts and tinctures of cannabis are grouped together in Schedule I of the 1961 United Nations Single Convention on Narcotic Drugs. Cannabis plant and resin are also included in Schedule IV of this Convention, which contains substances that are particularly liable to abuse and to produce ill- effects, and do not have therapeutic advantages that offset these effects.

A pre-review of cannabis and cannabis resin was carried out at the fortieth meeting of the ECDD, at which time the Committee recommended a critical review. Prior to this, cannabis had never been subject to a formal review by WHO.

Similarity to known substances and effects on the central nervous system
The consumption of cannabis can induce euphoria, laughter and talkativeness, change sensory and time perception, and compromise motor control and judgement.

Cannabis can stimulate appetite and produce dry mouth and dizziness. Acute cannabis use impairs certain types of cognitive function such as attention, learning and memory.

Dependence potential
In controlled laboratory studies, experienced cannabis users readily smoke cannabis and choose higher over lower doses. Human subjects can be trained to readily discriminate cannabis smoke from placebo smoke. Self-reported subjective effects associated with smoked cannabis in laboratory studies include dose-dependent increases in ratings of "drug effect", "high" or "stoned". Similar effects are produced by Δ9-THC alone when administered orally or when smoked, indicating that the cannabis constituent responsible for the plant’s reinforcing effects is Δ9-THC. The CB1 receptor antagonist, rimonabant, was shown, at least in some instances, to reverse the intoxication induced by cannabis.

International clinical diagnostic guidelines recognize the existence of cannabis dependence: this includes the development of withdrawal symptoms upon cessation of regular use. Symptoms of withdrawal include mood changes, irritability, increased anger, anxiety, craving, restlessness, sleep impairment, gastrointestinal disturbance and decreased appetite, with most individuals reporting four or more symptoms. These symptoms typically occur within 1 to 2 days of stopping regular use, usually peak 2 to 6 days after last use, and may last for 2 to 3 weeks. While dependence may develop as a result of regular use of cannabis with a low percentage of Δ9-THC, regular use of cannabis with a high percentage of Δ9-THC is associated with a greater severity of withdrawal symptoms. Approximately 1 in 10 cannabis users develop a cannabis use disorder, but this figure varies between studies and countries. The rates of cannabis use and of cannabis use disorder differ considerably between countries and in different regions of each country. Cannabis use disorder is most common in people under 30 years of age.

Actual abuse and/or evidence of abuse
Preclinical studies suggest that a lethal dose of cannabis and cannabis resin is not likely to be obtainable by humans and there is insufficient evidence to suggest that cannabis use increases overdose lethality from other drugs like opioids. Cardiovascular effects following acute administration, such as tachycardia and increased blood pressure, appear minimal or transient, and subside with tolerance. Some studies have suggested a link between cannabis use and heart attack, but the association is uncertain.

Young children may be particularly vulnerable to the effects of cannabis. Case reports indicate that young children who accidentally ingest cannabis can experience respiratory depression, tachycardia and temporary coma.

Cannabis consumption causes euphoria and can alter time perception. Some users may experience anxiety and panic reactions. Acute cannabis intoxication can precipitate a short-lasting psychotic state which reverses once the effects of the drug have abated.

Cannabis intoxication can impair cognitive function with effects including decreased attention and short-term memory. Cannabis use can impair driving, leading to a low-to-moderate (20–30%) increase in the risk of accidents. Cannabis use impairs reaction time, lane control, speedometer monitoring, hand and body steadiness and braking time as well as promoting inappropriate responses in an emergency scenario.

In addition to the acute effects of cannabis, there are effects of long-term use. Cannabis use in young people has been associated with an increased risk of developing psychotic disorders, although the relationship is complex and likely to be moderated by genetic factors. Women who smoke cannabis during pregnancy give birth to babies with birth weights that are, on average, lower than those of women who do not smoke cannabis during pregnancy. Cannabis smoking has been reported to lead to a 2.5-fold increase in the risk of testicular cancer.

Therapeutic usefulness
Cannabis has shown both positive outcomes and a lack of significant effect in the treatment of loss of appetite associated with HIV/AIDS, chronic pain, Crohn’s disease, diabetic neuropathy, neuropathic pain, migraine and cluster headaches, and Parkinson’s disease. Further data are required to enable full assessment of the efficacy of cannabis; however, studies have shown its possible value in a variety of therapeutic indications.

Cannabis preparations are currently subject to the same level of control as cannabis under the 1961 Single Convention on Narcotic Drugs, Article 2, Paragraph 3. Preparations of cannabis are used in the control of muscle spasticity associated with multiple sclerosis, which are not always controlled by other medications. Some patients with chronic pain have also been shown to obtain relief from cannabis preparations when other available medications have not been effective.

Preclinical reports indicate that cannabinoids reduce cancer cell proliferation, inducing apoptosis in these cells, as well as inhibiting cancer cell migration and angiogenesis in numerous cancer cell types. Cannabinoids and cannabis use have also been shown to have immunosuppressant and anti- inflammatory effects in laboratory animals and humans, respectively. These findings suggest other possible therapeutic applications for cannabis and cannabinoids.

Cannabis and cannabis resin are not included in the WHO EML or the WHO Model List of Essential Medicines for Children.

Recommendation
In the 1961 Single Convention on Narcotic Drugs, cannabis and cannabis resin are described, respectively, as the flowering or fruiting tops of the cannabis plant (excluding the seeds and leaves when not accompanied by the tops) from which the resin has not been extracted and as the separated resin, whether crude or purified, obtained from the cannabis plant. Reference to cannabis will be taken to also include cannabis resin. Of the many compounds in cannabis, delta-9- tetrahydrocannabinol (Δ9-THC) is the principal psychoactive constituent, while cannabidiol is also present but is not psychoactive.

Following the consumption of cannabis, the adverse effects experienced include dizziness and impairment of motor control and cognitive function. As a result of its effects on movement and cognition, cannabis use can impair driving ability. These acute adverse effects of cannabis consumption are similar to those produced by Δ9-THC alone. There are particular risks associated with cannabis exposure in young children, such as respiratory depression, tachycardia and coma.

Various adverse effects are associated with long-term cannabis use, particularly an increased risk of mental health disorders such as anxiety, depression and psychotic illness. Chronic regular cannabis use is particularly problematic for young people because of its effects on the developing brain.

Cannabis can cause physical dependence in people who use the drug daily or near daily. This is evidenced by the onset of cannabis withdrawal symptoms that occur upon abstinence; these symptoms include gastrointestinal disturbance, appetite changes, irritability, restlessness and sleep impairment. Clinical diagnostic guidelines such as the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) and the International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10) recognize cannabis dependence and other disorders related to cannabis use.

The Committee considered information regarding the therapeutic indications for cannabis and ongoing research into its possible medical applications. Several countries permit the use of cannabis for the treatment of medical conditions such as chemotherapy-induced nausea and vomiting, pain, sleep disorders and spasticity associated with multiple sclerosis. The Committee recognized the limited robust scientific evidence on the therapeutic use of cannabis. However, some oral pharmaceutical preparations of cannabis have therapeutic advantages for treatment of conditions such as certain forms of pain and epilepsy. Preparations of cannabis are defined as a mixture, solid, or liquid containing cannabis and are generally subject to the same control measures as cannabis and cannabis resin as per Article 2.3 of the 1961 Single Convention on Narcotic Drugs.

Cannabis and cannabis resin are included in Schedule I and Schedule IV of the 1961 Single Convention on Narcotic Drugs. Substances that are included in both these Schedules are particularly liable to abuse and to produce ill-effects and have little or no therapeutic use. Other substances that are included in both Schedules I and IV are fentanyl analogues, heroin and other opioids that are considered especially dangerous. Use of all these substances is associated with a significant risk of death, whereas cannabis use is not associated with such risk.

The evidence presented to the Committee did not indicate that cannabis and cannabis resin were particularly liable to produce ill-effects similar to the effects of the other substances in Schedule IV of the 1961 Single Convention on Narcotic Drugs. In addition, preparations of cannabis have shown therapeutic potential for treatment of pain and other medical conditions such as epilepsy and spasticity associated with multiple sclerosis, which are not always controlled by other medications. Cannabis and cannabis resin should therefore be scheduled at a level of control that will prevent harm caused by their use but, at the same time, will not act as a barrier to access and to research and development of cannabis- related preparations for medical use.

The Committee concluded that cannabis and cannabis resin do not meet the criteria for placement in Schedule IV.

The Committee then considered whether cannabis and cannabis resin were better placed in Schedule I or Schedule II of the 1961 Single Convention on Narcotic Drugs. While the Committee did not consider that cannabis is associated with the same level of risk to health as that posed by most of the other drugs placed in Schedule I, it noted the high rates of public health problems arising from cannabis use and the global extent of such problems. For these reasons, it recommended that cannabis and cannabis resin continue to be included in Schedule I of the 1961 Single Convention on Narcotic Drugs.

Recommendation: The Committee recommended that cannabis and cannabis resin be deleted from Schedule IV of the 1961 Single Con- vention on Narcotic Drugs.

Translated Technical Report Series

Translated Technical Report Series
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