Abuse of anti muscarinic drugs A review of the literature has suggested that

antimuscarinic drugs, notably trihexyphenidyl , benzatropine [benztropine], biperiden and orphenadrine , have been used for mood elevations or psychedelic experiences.

Antimuscarinic agents , used in the treatment of neurological conditions and the extrapyramidal adverse effects of neuroleptics, seem to have antidepressant actions , both directly and by enhancing the effects of psychostimulants . However the mechanism of action is unclear. ch olinergic and dopaminergic systems in the CNS may have antagonistic actions. Thus , dopamine receptor blockade with neuroleptics may lead to compensatory cholinergic 'overdrive ' resulting in anxiety , which may be 'corrected ' by a high dose of antimuscarinic drugs. Muscarinic cholinergic systems may interact with the GABA­benzodiazepine receptor complex and it is possible that antimuscarinic agents produce anxiolyt ic effects via this mechanism. Studies using animal models suggest that antimuscarinic agents may modify drive behaviour and increase the hedonic capacity of Individuals.

There is some evidence that depression possibly arising from abnormal interactions between CNS cholinergic-aminergic systems, may be improved by antimuscarinics .

Long term use of antimuscarinic drugs can result in tolerance and withdrawal symptoms upon cessation of drug use e.g. myalgias, malaise, coryza, diaphoresis , paraesthesias, gastrointestinal disturbances, headache, insomnia, anxiety, nightmares, fatigue , dysphoria and a 'rebound ' deterioration of the parkinsonian or extrapyramidal adverse effects being treated by these drugs. Thus, gradual withdrawal of anticholinergic medication is recommended . These tolerance and withdrawal syndrome effects are the result of neuronal adaptations of long term postsynaptic antimuscarinic blockade , up-regulation of receptor sites and the development of supersensitivity of the cholinergic system.

Other mood altering drugs e.g. cannabinoids, barbiturates , opiates and ethanol antagonise cholinergic mechanisms by inhibition of acetylcholine release from the presynaptic nerve terminal. Thus , these drugs have additive effects when used in conjunction with antimuscarinics .

Considering the potent ial for abuse of " , , agents directly antagonizing the action of acetylcholine at the postsynaptic muscarinic receotor', careful selection of antimuscarinic agents with different pharmacological actions that minimise their 'attractiveness ' as a substance of abuse is recommended . Dilsaver SC Journal 01 Clinical Psychopharmacology 8 14·22, Feb 1988 [77 references) .. ,

0157-727/ / 88/ 0416-0003/ 0$01 .00/ 0 © ADIS Press REACTIONS'" 16 April 1988 3