Medicinal Uses of Cannabis

Recent years has seen the identification of an endocannabinoid system in the body that regulates neurotransmission release in various physiological processes, including memory, appetite, immune responses and pain sensation.

The most common endocannabinoids in the body are N-arachidonoylethonalamide (anandamide, AEA) and 2-arachidonoylglycerol (2-AG) that act on specific cannabinoid receptors (CB1 and CB2). CB1 receptors are mainly present in the central and peripheral nervous system and are major mediators of health and disease, while CB2 receptors have prevalence in the peripheral tissues of the immune system. Endocannabinoids are inactivated by hydrolysis by the enzyme, fatty acid amine hydrolase (FAAH).

Cannabis Sativa also known as ganja originated in Central and South Asia. The chemical composition of the plant varies with the type, age, part of plant and method of preparation used. With over sixty cannabinoids as well as other constituents, the plant has demonstrated specific medicinal activity including analgesia, anti-inflammatory, anti-tumour, anti-oxidant and neuroprotective. Activation of cannabinoids are mediated mainly by activation of the CB1 and or CB2 receptors. A novel cannabinoid receptor has also been identified that is implicated in many of the effects of Cannabidiol. These receptors facilitate the physiological activity of ganja.

TOXICOLOGY AND PHARMACOLOGY OF CANNABIS

Though there are more than 400 chemical compounds in the cannabis plant, the cannabinoids have been the most studied; especially delta-9-tetrahydrocannabinol (THC), delta-8-tetrahydrocannabinol (delta-8-THC), cannabidiol (CBD) and cannabinol (CBN). THC produces most of the well-known effects of ganja, but it interacts with the others to modify the results. THC, the most psychoactive ingredient of the plant, is a part of some of the preparations made from the plant. However, the percentage varies.

Natural and most synthetic cannabinoids are oily and soluble in fat, but only slightly soluble in water. The pharmacological effects of cannabinoids depend on the medium used to administer them.

In order to understand the effects of substances derived from cannabis, the dosage has to be controlled. The quantity of THC present in a sample delivered by smoking depends on the genetic background (the genotype) of the plant, the sex of the plant, conditions of growth and storage, and sample preparation. Also, a significant proportion of the THC that is found in the fresh leaves is in the inactive carboxylated form and this can be detected by gas-liquid chromatography (GLC).

Decarboxylation to the active THC occurs slowly during storage and rapidly during heating, as in smoking or in GLC analysis. Moreover, the way a cigarette is smoked determines the amount of THC absorbed by the smoker.

Metabolic Effect

When THC is ingested, very little reaches the brain, but most is accumulated in the liver, kidneys and lungs. As THC is fat-soluble, some of it tends to accumulate longer in the fat deposits in the body, hence the complete elimination of a single dose of the drug takes about one week and it is eliminated mostly in the urine and faeces, but not through the salivary glands.

Cannabinoid metabolites can be found in the blood and urine for up to one month after exposure to ganja. The test can be positive for three days after a single use of cannabis. Secondary exposure to the smoke through inhalation is enough to produce positive urine test results. In chronic cannabis users, a urine test can detect residual positive levels for up to six weeks after the last use. As a result, a positive urine test for a chronic user does not necessarily indicate recent or continued use. A test was recently developed by Schwilke et al. which allows the differentiation of residual cannabinoid excretion in chronic users and new cannabis use.

Pharmacology

Pharmacologically THC is not a narcotic, although considered so by law. In the pharmacological sense, a narcotic induces trance-like or calm state and allows one to become indifferent to pain. Ganja is therefore better described as an intoxicant, a hallucinogen or a euphoriant.

To eliminate the unwanted effects of the drug, the molecule can be modified. Some of the synthetic analogues are even more potent than THC itself. The intensity and duration of effects in relation to dosage is still to be determined. These factors depend on the concentration of the drug, which is determined by the dose, the route of administration and the mechanisms of interaction. Another important determinant is the physiological state of the person being affected and the sensitivity of relevant cells.

THC interacts with common drugs. It increases the depressive effects of psycho depressants like alcohol, sedatives and opiates. These inter- actions are most likely mediated by the brain. Interactions of THC and stimulants like caffeine, nicotine and cocaine are complex, with occurrence of addictive and conflicting effects, depending on dosage and time intervals between ingestion.

A notable and rapid tolerance to most of the physical (functional) and psychological effects of THC develops in animals and man. This tolerance, which has a metabolic and tissue component, may not develop into some of the non-specific cellular effects of the drug. There is some cross-tolerance between THC and ethanol, and between THC and barbiturates. Withdrawal symptoms develop after termination of heavy cannabis administration on a daily basis. These symptoms are more noticeable after pure administration.

THC has been classified among the dependence-producing drugs that have the following characteristics.

They:

  • induce symptoms of reversible neuropsychological and neuro-behavioural toxicity;
  • induce a primary pleasurable reward and diffuse unpleasant feelings;
  • intensify or induce craving for the drug and drug-oriented behaviour; and
  • Induce tolerance.

Abrupt interruption is associated with some withdrawal symptoms.

Long-term use is associated with increased incidents of mental impairment.

Pharmacokinetics

The absorption, distribution, metabolism and elimination of delta-9- THC is dependent on the length of time that THC and its metabolites remain in the body. No significant difference has been found in the metabolism, disposal and kinetics of THC between the human male and female. The absorption, distribution, metabolism and secretion of cannabis within the human body depend on the method of administration and potency of the specific plant. THC is absorbed into the blood faster when ganja is smoked than when it is taken orally because of the large surface area of the lungs.

Toxicity

Cannabis has been in use for about 6,000 years and it still remains a relatively safe drug. The toxicity of the cannabis resin and of THC is low. There have been very few reports of death by overdose. Furthermore, there was no proof that these deaths were due to THC. In Britain, for example, more than 100,000 alcohol-related deaths and at least as many tobacco-related deaths occur each year. Also, commonly used drugs such as aspirin, paracetamol and some non-steroidal anti-inflammatory compounds are not safe in some cases as they may cause gastric bleeding and liver damage. It should be noted though, that no drug is free of toxic effects, so the risks always have to be balanced against the benefits.

Most pharmacological studies have focused on the toxic effects of cannabis on the central nervous system (CNS) and as such, acute cannabis toxicity results in difficulty with coordination, decreased muscle strength, decreased hand steadiness, postural hypotension, lethargy, decreased concentration, slowed reaction time, slurred speech and conjunctival injection.

Continued research is needed on other cannabinoids and more acceptable administration of cannabis to prevent the adverse pulmonary effects, associated with smoking. However, these research developments have to be balanced against the restrictive public policy decisions of government agencies.