Side effects of pharmaceuticals not elicited by comparable herbal medicines: the case of tetrahydrocannabinol and marijuana.

OBJECTIVE:

Herbalists claim that the polypharmacy of botanical remedies provides 2 advantages over single-ingredient drugs: (1) primary active ingredients in herbs are synergized by secondary compounds, and (2) secondary compounds mitigate the side effects caused by primary active ingredients. To examine this second claim, medical marijuana was compared with its primary active ingredient, tetrahydrocannabinol.

DATA SOURCES:

A search on MEDLINE (1966-1999), AGRICOLA (1990-1999), and Biological and Agricultural Index (1964-1999) using keywords “cannabinoids,” “marijuana,” “tetrahydrocannabinol,” “Cannabis,” and “hemp.” Phytochemical and ethnobotanical data were searched with the Agricultural Research Service database. Unindexed botanical journals were scanned by hand.

STUDY SELECTION:

Studies documenting the efficacy of secondary compounds mitigating side effects of tetrahydrocannabinol consisting of double-blind trials, unblinded studies, animal models, and in vitro experiments.

DATA EXTRACTION AND DATA SYNTHESIS:

Data validity was assessed by consensus, weighted by source (peer-reviewed article vs popular press), identification methodology (analytical chemistry vs clinical history), and frequency of independent observations.

CONCLUSIONS:

Good evidence suggests that some side effects of tetrahydrocannabinol are mitigated by other volatile compounds present in the essential oil of marijuana. Inhaling tetrahydrocannabinol, which avoids first-pass hepatic metabolism, has advantages over ingesting it. Other cannabinoids, terpenoids, and flavonoids can reduce tetrahydrocannabinol-induced anxiety, cholinergic deficits, and immunosuppression. Other compounds increase cerebral blood flow, enhance cortical activity, kill respiratory pathogens, and provide anti-inflammatory activity. The hazards of marijuana smoke can be reduced with appropriate technology. Proprietary Cannabis extracts containing a mixture of cannabinoids, terpenoids, and flavonoids are currently being developed and tested.