Section 2) Pharmacology.

Contrary to prior assertions by the DEA, the chemistry, toxicology, and pharmacology of marijuana has been subjected to extensive study and peer review, and have been well-characterized in scientific literature.

The effects of marijuana smoke on the lungs have been extensively studied. While marijuana smoke has more tar and carbon monoxide than tobacco smoke, in several other areas marijuana smoke is demonstrably less harmful than tobacco smoke, as in effect on small airway function, effect on bronchoalveolar lavage (BAL) macrophages, effect on phagocytic behavior or the respiratory burst of human pulmonary alveolar macrophages, and oxidant release of pulmonary alveolar macrophages. The tar in marijuana smoke can be reduced by filtration (such as with a waterpipe), and many gas-phase cytotoxins in the smoke are water soluble. The carbon monoxide levels produced by marijuana smoke are influenced by breathholding, which provides a diminishing return in contributions to plasma levels of the drug's active ingredient and thus can be reduced by changes in smoking techniques. Efforts to promote safer marijuana use through the use of waterpipes and changes in smoking habits are impossible under existing, schedule 1 based, policy.

The absorption of THC from marijuana smoke is well characterized, and variables such as dosage stability, route of administration, bioavailability, puff volume, THC content, and breathholding time have all been investigated for their effect on absorption.

The pharmacology, toxicology, and chemistry of marijuana and its constituent chemicals have been published in scientific journals, and structure activity relationships for the cannabinoids have been established and correlated with animal tests. A stable pharmacological profile of the substance's effects is available, as is epidemiological data on the incidence and prevalence of minor side effects. The substance has a well-established and extremely low toxicity. There are no cases of overdose on record.

This knowledge allows scientists to make valid assertions about marijuana on the basis of research on its separate constituent parts.

Prior hypotheses that marijuana's mechanism of action involved cell membrane perturbation have been abandoned by the scientific community on two grounds, 1) extremely serious problems with method affect the validity of findings supporting the hypotheses, and 2) a receptor-based mechanism of action has been determined, localized, and characterized over the last seven years.

References Cited in Section 2.

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Azorlosa, J., Heishman, S., et al., "Marijuana Smoking: Effect of Varying D9-Tetrahydrocannabinol Content and Number of Puffs." Journal of Pharmacology and Experimental Therapeutics. 261:114-122. 1992.

Barbers, R.G., Evans, M.J., Gong, H., and Tashkin, D.P., "Enhanced Alveolar Monocytic Phagocyte (Macrophage) Proliferation in Tobacco and Marijuana Smokers." Am Rev Respir Dis. 143:1092-1095, 1991.

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U.S. Department of Justice, Drug Enforcement Administration, Docket No. 86-22. Marijuana Scheduling Petition, Denial of Petition. 54 Fed. Reg. 53,787 (1989)

U.S. Department of Justice, Drug Enforcement Administration, Docket No. 86-22. Marijuana Scheduling Petition, Denial of Petition; Remand. 57 Fed. Reg. 10,499 (1992)

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