INTERPRETATION A single THC administration induces psychotic , negative , and other psychiatric symptoms with large effect sizes .
There is no consistent evidence that CBD induces symptoms or moderates the effects of THC .
BACKGROUND Approximately 188 million people use cannabis yearly worldwide , and it has recently been legalised in 11 US states , Canada , and Uruguay for recreational use .
The potential for increased cannabis use highlights the need to better underst and its risks , including the acute induction of psychotic and other psychiatric symptoms .
We aim ed to investigate the effect of the cannabis constituent Δ9-tetrahydrocannabinol ( THC ) alone and in combination with cannabidiol ( CBD ) compared with placebo on psychiatric symptoms in healthy people .
Does olanzapine inhibit the psychomimetic effects of Δ9-tetrahydrocannabinol?
Δ9-Tetrahydrocannabinol ( THC ) produces transient psychomimetic effects in healthy volunteers , constituting a pharmacological model for psychosis . The dopaminergic antagonist haloperidol has previously been shown to reduce these effects . This placebo-controlled , cross-over study in 49 healthy , male , mild cannabis users aim ed to further explore this model by examining the effect of a single oral dose of olanzapine ( with dopaminergic , serotonergic , adrenergic , muscarinergic and histaminergic properties ) or two oral doses of diphenhydramine ( histamine antagonist ) on the effects of intrapulmonarily administered THC .  Transient psychomimetic symptoms were seen after THC administration , as measured on the positive and negative syndrome scale ( 20.6 % increase on positive subscale , p<0.001 ) and the visual analogue scale for psychedelic effects ( increase of 10.7 mm on feeling high ) . Following the combination of THC and olanzapine , the positive subscale increased by only 13.7 % and feeling high by only 8.7 mm . This reduction of THC effects on the positive subscale failed to reach statistical significance ( p=0.066 ) . However , one-third of the subjects did not show an increase in psychomimetic symptoms after THC alone . Within responders , olanzapine reduced the effects of THC on the positive subscale ( p=0.005 ) . Other outcome measures included pharmacokinetics , eye movements , postural stability , pupil/iris ratio , and serum concentrations of cortisol and prolactin
INTERPRETATION A single THC administration induces psychotic , negative , and other psychiatric symptoms with large effect sizes .
There is no consistent evidence that CBD induces symptoms or moderates the effects of THC .
BACKGROUND Approximately 188 million people use cannabis yearly worldwide , and it has recently been legalised in 11 US states , Canada , and Uruguay for recreational use .
The potential for increased cannabis use highlights the need to better underst and its risks , including the acute induction of psychotic and other psychiatric symptoms .
We aim ed to investigate the effect of the cannabis constituent Δ9-tetrahydrocannabinol ( THC ) alone and in combination with cannabidiol ( CBD ) compared with placebo on psychiatric symptoms in healthy people .