The administration of psilocybin to healthy hallucinogen experienced volunteers

The administration of psilocybin to healthy,hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability

This study sought to assess the tolerability of intravenously administered psilocybin in healthy, hallucinogen-experienced volunteers in a mock-magnetic resonance imaging environment as a preliminary stage to a controlled investigation using functional magnetic resonance imaging to explore the effects of psilocybin on cerebral blood flow and activity.

The present pilot study demonstrated that up to 2 mg of psilocybin delivered as a slow intravenous injection produces short-lived but typical drug effects that are psychologically and physiologically well tolerated. With appropriate care, this study supports the viability of functional magnetic resonance imaging work with psilocybin.

Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is a tryptamine hallucinogen and the pro-drug of psilocin (4-hydroxy-N,N-dimethyltryptamine), a partial agonist at the 5-HT2A receptor (Nichols, 2004) and the active constituent of psilocybe mushrooms.

In the late 1950s, psilocybin was identified and isolated from its natural source (Hofmann et al., 1958, 1959). Like the pharmacologically related hallucinogen, lysergic acid diethylamide (LSD), psilocybin was commonly used as an adjunct to psychoanalytic psychotherapy for the treatment of a wide range of psychiatric conditions (Grinspoon and Bakalar, 1979; Leuner, 1963).

In the mid-1960s, the popularization of hallucinogenic drugs stimulated an increase in recreational use. Subsequent adverse events attracted media attention and public and political concern, leading to the withdrawal of production (Spencer, 1966) and the introduction of significant restrictions on research (Lee and Shlain, 1985).

It has only been in the last 15 years or so that clinical researchers have begun to work again with this group of compounds (Griffiths et al., 2006; Vollenweider et al., 1997). Functional MRI (fMRI) has emerged as a powerful imaging modality, but psilocybin has never been administered in this environment. Recent guidelines for human research with hallucinogens cautioned against exposing ‘intoxicated’ subjects to potentially anxiogenic situations (Johnson et al., 2008).

In accordance with this advice, the present study sought to assess the tolerability of intravenously administered psilocybin in healthy, hallucinogen-experienced volunteers in a mock-fMRI setting as a preliminary stage to a controlled investigation using this imaging modality. Intravenous administration was chosen on the basis of previous work indicating good tolerability and a fast onset and brief dura- tion of subjective effects (Hasler et al., 1997), convenient for fMRI studies.

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