Review of the Validity and Significance of Cannabis Withdrawal Syndrome

Budney, Alan J.; Hughes, John R.; Moore, Brent A.; Vandrey, Ryan G.

doi:10.1176/appi.ajp.161.11.1967

Cited by 441 publications

(397 citation statements)

References 48 publications

(115 reference statements)

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“…First, since participants were tested after 24 h of abstinence, it is unclear whether THC withdrawal may have accounted for the observed findings. However, most heavy cannabis users do not display peak withdrawal symptoms until 2-3 days following the cessation of use (Budney et al, 2004), which most likely precludes the possibility that the current results were due to cannabis withdrawal. However, a related confound is that participants in the current experiment were not monitored during the 24 h abstinence window.…”

Section: Discussionmentioning

confidence: 87%

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

Skosnik

Edwards

O’Donnell

et al. 2007

Neuropsychopharmacol

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While the cerebellum contains the highest density of cannabinoid receptor (CB1) in the brain, no studies have assessed the effect of exogenous cannabinoids on cerebellar-dependent learning in humans. The current study, therefore, examined the effect of chronic cannabis use on classical eyeblink conditioning (EBC), a cerebellar-mediated task which has been shown to be disrupted in CB1 knockout mice. Chronic cannabis users (24 h abstinence before study; positive THC urine drug test) free of DSM-IV Axis-I or -II disorders, were evaluated. A delay EBC task was utilized, in which a conditioned stimulus (CS; 400 ms tone) co-terminated with a corneal air puff unconditioned stimulus (US; 50 ms), thus eliciting a conditioned blink response (CR). The cannabis group exhibited markedly fewer, and more poorly timed CRs as compared to drug-naive controls. There were no differences between the groups in either the unconditioned response (UR) or an EEG measure of selective attention to the CS (N100 auditory ERP), indicating that the disruption observed in the cannabis group was specific to CR acquisition. These results suggest that cannabis use is associated with functional deficits in the cerebellar circuitry underlying EBC, a finding which corroborates the recent work in CB1 knockout mice.

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Section: Discussionmentioning

confidence: 87%

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

Skosnik

Edwards

O’Donnell

et al. 2007

Neuropsychopharmacol

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“…We aimed to exclude any cannabis users exhibiting the cannabis withdrawal syndrome, which has been identified in a subset of very frequent (i.e., daily) cannabis users, beginning as early as 5 to 6 h after last use and lasting up to several weeks in the presence of abstinence (Budney et al 2004). Participants identified as daily cannabis users on the TLFB, and who last used cannabis more than 5 h previously, were administered a modified, interviewer-rated version of the Cannabis Withdrawal Checklist (Budney et al 1999) to rule out the presence of cannabis withdrawal syndrome.…”

Section: Participantsmentioning

confidence: 99%

Association of abnormal semantic processing with delusion-like ideation in frequent cannabis users: an electrophysiological study

et al. 2012

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Rationale-Frequent cannabis use is a risk marker for schizophrenia and delusions, but the neurocognitive mechanisms of this relationship remain unclear.Objectives-We sought evidence that cannabis users have deficits in processing relationships between meaningful stimuli, similar to abnormalities reported in schizophrenia, and that these deficits are associated with delusion-like ideation. We used the N400 event-related brain potential (ERP) waveform as a neurophysiological probe of activation of concepts in semantic memory. We hypothesized that cannabis users would exhibit larger (more negative) than normal N400 amplitudes in response to stimuli meaningfully related to a preceding prime-reflecting deficient activation of concepts related to the prime. We further hypothesized that the magnitude of this abnormality would correlate with severity of delusion-like ideation.Methods-We recorded ERPs in 24 frequent cannabis users and 24 non-using comparison participants who viewed prime words followed by targets which were either words related or unrelated to the prime or pronounceable non-words. The participants' task was to indicate whether the target was a word. Delusion-like ideation was measured via the Schizotypal Personality Questionnaire.Results-Contrary to our hypothesis, cannabis users exhibited smaller than normal N400s to both related and unrelated targets. These abnormalities correlated with delusion-like ideation in cannabis users only. Conclusions-The results are consistent with a generalized abnormality of activation within semantic memory neural networks in cannabis users. Further research is needed to investigate whether such an abnormality plays a role in the development of delusion-like ideation in cannabis users.

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“…Since marijuana withdrawal was not formally measured in this study, it is certainly possible that subjects were experiencing symptoms of marijuana withdrawal (which include GI discomfort) during the trial when they tried to stop or cut down (Budney et al, 2004) Although marijuana use did not significantly decline during the trial, any attempt to cut down or stop marijuana use may have resulted in withdrawal symptoms. It is known that marijuana (through CB1 activity) can reduce gut motility and thereby prolong exposure of atomoxetine to gastrointestinal mucosa, possibly leading to GI irritation that could further compound withdrawal related GI symptoms.…”

Section: Discussionmentioning

confidence: 99%

Atomoxetine for treatment of marijuana dependence: A report on the efficacy and high incidence of gastrointestinal adverse events in a pilot study

Tirado

Goldman

Lynch

et al. 2008

Drug and Alcohol Dependence

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Marijuana users consistently demonstrate impairments in attention, executive function and response inhibition, which resemble deficits seen in attention deficit hyperactivity disorder (ADHD). We hypothesized that targeting the cognitive deficits associated with chronic marijuana use through ADHD medications may help identify a therapeutic agent for marijuana dependence.Thirteen subjects participated in an 11-week open label study to determine the feasibility, safety and tolerability of atomoxetine for individuals seeking treatment for marijuana dependence. The Time-Line Follow-Back measured marijuana use 90 days prior to study entry (p-TLFB) and weekly during the study (s-TLFB) along with weekly qualitative urine drug screen (UDS). For the eight subjects who completed the trial, the TLFB data showed a trend toward reduction in use with an increase in percent days abstinent (p=0.06). Analysis of weekly UDSs did not confirm the TLFB trend with 94% of all possible UDSs positive for THC through out the study.Marijuana dependent subjects taking atomoxetine experienced an inordinate number of gastrointestinal (GI) adverse events. Overall, 10 of 13 subjects (77%) experienced a mild to moderate GI adverse event defined as nausea, vomiting, dyspepsia, and loose stools. Atomoxetine is of limited utility in the treatment of cannabis dependence and is associated with clinically significant GI adverse events.

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Review of the Validity and Significance of Cannabis Withdrawal Syndrome

Cited by 441 publications

References 48 publications

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

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

Association of abnormal semantic processing with delusion-like ideation in frequent cannabis users: an electrophysiological study

Atomoxetine for treatment of marijuana dependence: A report on the efficacy and high incidence of gastrointestinal adverse events in a pilot study

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