APPENDIX 5

Pharmacology of Cannabis

1. Cannabis is the generic name for Indian Hemp (C. sativa). Cannabis drugs are obtainable from the flowing tops or leaves of the plant. The resin of C. sativa is often referred to as hashish and its constituents include cannabidiol, cannabinol and several tetrahydrocannabinols referred to collectively as T.H.C. Other constituents are cannabigerol, cannabichromene and cannabidiolic acid. The active principles are T.H.C., two of them. D l and D 6 T.H.C., being of great potency. The relations between the constituents and the possibilities of interconversion between some of them under different conditions such as the high temperature and degree of oxygenation that occur during smoking have been studied but are not as yet fully elucidated. Work is hindered by the relative insolubility of these substances. The relative and total amounts of the active principles in a sample of cannabis depend upon climatic factors during growth, processing or preparation and the form in which the drug is used. For example, D 6 T.H.C. is approximately 2-5 times as active when smoked as it is when swallowed. The rate and degree of absorption and hence the onset and duration of effect are related to the route of administration (inhalation being faster than oral administration) and the expertise of the smoker in prolonging contact between the smoke and the absorptive surfaces of the lung, etc. In man inhaled smoke initiates effects within a few minutes and a maximal effect may be obtained after a half to one hour. By inhalation a certain degree of control is attained according to the effect desired. The action persists for some 3-5 hours.

2. Chemical methods of analysing the constituents and products of hashish include chromatographv and spectrophotometry. Quantitative isolation of the active principles or their metabolites from body fluids is at present not possible and consistent recoveries cannot yet be guaranteed. There is no precise knowledge about absorption, distribution, mode of action or metabolic degradation of the T.H.C. or the other constituents of cannabis in man.

3. In animals gross overdosage with cannabis causes death from respiratory depression. Cannabis prolongs the sleeping time of mice treated with hypnotic doses of barbiturates and this effect is said to persist over a period of 2-3 months. Such a prelonged effect suggests that cannabis has interfered with adaptive lysosomal enzyme systems. Cannabis also intensifies the stimulant effect of amphetamine in mice as judged by the degree of restlessness produced, another effect which may be due to inhibition of hepatic enzymic activity. Whether these two important interactions occur in man is not known. Pharmacological research on man is at present severely limited by the existing drug laws and regulations.