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CLINICAL STUDY: Cannabimimetic effects modulated by cholinergic compounds


John M. McPartland, Department of Family Medicine, College of Medicine, University of Vermont, 53 Washington Street Ext., Middlebury, VT 05753, USA. E-mail:


This report is based upon a clinical case series describing five patients who volitionally adultered cannabis with a variety of compounds that shared a common trait—cholinergic modulation. They included a nicotinic agonist, muscarinic antagonist and antiacetylcholinesterase compounds. Some of these compounds (e.g. tobacco) are known to exert pharmacokinetic effects upon cannabinoids (e.g. improved drug absorption). Contrarily, our patients claimed that the compounds altered pharmacodynamic ‘cannabimimetic’ effects. The case series was supported by forensic identification of adulterants and by use of a symptom causality algorithm. A survey of the gray literature and drug culture web sites indicated that the case series portended a larger social phenomenon. Furthermore, many clinical reports, animal behaviour studies and in vitro mechanistic studies substantiated our observations. In conclusion, we provide empirical data regarding a new trend in the drug culture—cholinergic modulation of cannabinoid effects—that presents new research directions.