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 .
Naltrexone does not attenuate the effects of intravenous Δ9-tetrahydrocannabinol in healthy humans.
Although a wealth of pre clinical evidence indicates an interplay between the μ-opioid ( MOR ) and cannabinoid 1 receptor ( CB1R ) systems , the precise nature of the cross modulation in humans is unclear . The objective of this study was to evaluate the effects of pretreatment with the MOR antagonist , naltrexone , on the subjective , behavioural and cognitive effects of the CB1R agonist , Δ9-tetrahydrocannabinol ( THC ) , in healthy human subjects . Healthy human subjects , screened carefully for any medical or psychiatric illness , were administered either placebo or active naltrexone ( 25 mg ) orally on each test day , followed 45 min later by placebo and 165 min later by active i.v . THC ( 0.025 mg/kg ) in a r and omized , fixed-order , double-blind manner . Subjective , behavioural and cognitive effects were assessed before and at several points after each drug administration . THC produced expected effects , including euphoria , anxiety , transient perceptual alterations , transient psychotomimetic effects and cognitive impairments .  However , naltrexone did not produce any effects alone , nor did it attenuate any of THC 's effects . Thus , in healthy human subjects who use cannabis intermittently , MOR antagonism does not modulate the common acute subjective , behavioural and cognitive effects of THC
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 .