Marijuana alters the human cerebellar clock

Abstract

The effects of marijuana on brain perfusion and internal timing were assessed using [15O] water PET in occasional and chronic users. Twelve volunteers who smoked marijuana recreationally about once weekly, and 12 volunteers who smoked daily for a number of years performed a self-paced counting task during PET imaging, before and after smoking marijuana and placebo cigarettes. Smoking marijuana increased rCBF in the ventral forebrain and cerebellar cortex in both groups, but resulted in significantly less frontal lobe activation in chronic users. Counting rate increased after smoking marijuana in both groups, as did a behavioral measure of self-paced tapping, and both increases correlated with rCBF in the cerebellum. Smoking marijuana appears to accelerate a cerebellar clock altering self-paced behaviors.

Cannabis Use Disrupts Eyeblink Conditioning: Evidence for Cannabinoid Modulation of Cerebellar-Dependent Learning

“…These results are in agreement with previous human work showing altered cerebellar activity during cannabis administration (Mathew et al, 1998;O'Leary et al, 2003). In addition to providing further evidence that cannabis use disrupts cerebellar function, the current findings provide an important clue about the specific role endocannabinoids may play in normal cerebellar-dependent learning, particularly in light of the recent study of delay EBC in CB1 knockout animals (Kishimoto and Kano, 2006).…”

“…In addition to its role in motor coordination, the cerebellum is thought to play a key role in temporal operations such as rhythm production, time estimation, and some forms of associative learning (Ivry and Keele, 1989;Katz and Steinmetz, 2002;Leiner et al, 1991). Indeed, altered time perception is one of the most frequently reported subjective experiences associated with acute cannabis intoxication (Hicks et al, 1984;Mathew et al, 1998), which is thought to be modulated by the cerebellum (O'Leary et al, 2003). Thus, studies examining cerebellar-mediated processes may provide important clues in relation to the subjective effects of cannabis and the role of the endocannabinoid system in normal brain function.…”

“…Of the experiments which have evaluated cannabinoid effects on time estimation, several have shown that direct cannabis administration induces temporal disintegration, which is typically exhibited in the form of increased internal clock speeds (the experience of time passing more slowly; Hicks et al, 1984;Mathew et al, 1998;O'Leary et al, 2003). In relation to cerebellar modulation of cannabis' effect on time perception, a study integrating behavioral measures of temporal processing with neuroimaging methodologies has yielded positive results.…”

“…In relation to cerebellar modulation of cannabis' effect on time perception, a study integrating behavioral measures of temporal processing with neuroimaging methodologies has yielded positive results. Using PET, O'Leary et al (2003) demonstrated that cannabis-induced alterations in a selfpaced timing task were correlated with the increased activity of medial cerebellar cortex. Interestingly, cerebellar metabolism during acute cannabis administration has been shown to correlate with subjective ratings of intoxication (Volkow et al, 1996).…”

Cannabinoid Receptor Activation Shifts Temporally Engendered Patterns of Dopamine Release

“…Although subjects report that cannabis makes time pass very slowly (Moreau de Tours, 1845; Tart, 1970), the majority of clinical studies on the subject reveal that cannabinoids increase the rate at which subjective time passes relative to clock time (Atakan et al, 2012;Hicks et al, 1984;O'Leary et al, 2003). This cannabinoid-induced acceleration of an internal clock likely contributes to subjects increasing self-timed behaviors, such as counting and tapping, and overestimating periods of elapsed time ( .…”