PSILOCYBIN & OCD
Research supporting psilocybin’s use in treating OCD
Despite a paucity of clinical trials investigating the anti-obsessional effect of psilocybin,
converging evidence from a number of sources, as well as an array of possible
mechanisms of action, lend support to its plausibility as a treatment. Although a
considerable number of user reports on the internet - and one critically acclaimed stand-
up comedy show, developed and performed by an OCD patient - attest to the efficacy of
psilocybin, their comparatively low evidentiary weight preclude their exploration here.
In a rodent model of OCD - marble burying behavior - Matsushima and colleagues
(2009) studied the effects both of psilocybin, and a solution of powdered Psilocybe
argentipes, in mice. While both synthetic psilocybin and the mushroom solution were
recorded to reduce marble burying without reducing general locomotor activity, this
study bears three points worthy of consideration. Firstly, compared to psilocybin, a
much smaller dose of mushroom extract was required to produce significant effects on
marble-burying, suggesting a partial therapeutic role for other components of P.
argentipes. The other psychoactive alkaloids found in the Psilocybe genus, baeocystin
and norbaeocystin, may exert independent effects, or interact with psilocin in an
‘entourage effect’. Secondly, other work investigating psilocybin in rodent models has
failed to detect any therapeutic benefit. Psilocybin produces no change in a rat model of
depression (Jefsen et al., 2019), despite strong antidepressive action being repeatedly
found in human trials. Further research is required to account for this difference, but it
may be that antidepressive action requires cognitive or psychological abilities lacking in
rodents (e.g., the perception and processing of awe or meaning), whereas anti-
obsessional effects are mainly driven by direct pharmacological mechanisms. Finally,
any proposed pharmacological model of the reduction of marble-burying should aim to
go beyond a simple account of agonism at one receptor, since P. argentipes did not
produce a proportional dose-response relationship, displaying instead an inverted ueffect..