Background: Cannabis use disorder (CUD) is a common condition with few treatments. Several studies in other substance use disorders have found that applying repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) decreases cue-elicited craving and possibly decreases use. To date, there have been no studies attempting to use rTMS in CUD. Objectives: This study was conducted to determine if rTMS could be feasibly delivered to a group of non-treatment seeking CUD participants. Secondarily, the study aimed to estimate the effect of rTMS on craving. Methods: In a double-blind, sham-controlled, crossover design, a single session of active or sham rTMS (Left DLPFC, 10 Hz, 110% rMT, 4000 pulses) was delivered during a validated cannabis cue paradigm. Participants crossed over to complete the other condition one week later. The feasibility and tolerability were measured by the rate of retention, and the percentage of participants able to tolerate full dose rTMS, respectively. Craving was measured using the Marijuana Craving Questionnaire (MCQ). Results: Eighteen non-treatment seeking CUD participants were recruited from the community; 16 (three women) completed the trial (89% retained for the three study visits). All of the treatment completers tolerated rTMS at full dose without adverse effects. There was not a significant reduction in the total MCQ when participants received active rTMS as compared to sham rTMS. Conclusion: rTMS can be safely and feasibly delivered to CUD participants, and treatment is well tolerated. A single session of rTMS applied to the DLPFC may not reduce cue-elicited craving in heavy cannabis users.

Focal Electrically-Administered Seizure Therapy (FEAST) is a form of electroconvulsive therapy (ECT) that spatially focuses the electrical stimulus to initiate seizure activity in right prefrontal cortex. Two open-label non-comparative studies suggested that FEAST has reduced cognitive side effects when compared to historical data from other forms of ECT. In two different ECT clinics, we compared the efficacy and cognitive side effects of FEAST and Right Unilateral Ultrabrief Pulse (RUL-UBP) ECT. Using a non-randomized, open-label design, 39 depressed adults were recruited after referral for ECT. Twenty patients received FEAST (14 women; age 45.2±12.7), and 19 received RUL-UBP ECT (16 women; age 43.2±16.4). Key cognitive outcome measures were the postictal time to reorientation and the Columbia University Autobiographical Memory Interview: Short-Form (CUAMI-SF). Antidepressant effects were assessed using the Hamilton Rating Scale for Depression (HRSD₂₄). In the Intent-to-treat sample, a repeated measures mixed model suggested no between group difference in HRSD₂₄ score over time (F_1,35 = 0.82, p=0.37), while the response rate favored FEAST (FEAST: 65%; RUL-UBP ECT: 57.9%), and the remission rate favored RUL-UBP ECT (FEAST: 35%; RUL-UBP ECT: 47.4%). The FEAST group had numeric superiority in average time to reorientation (FEAST: 6.6±5.0 minutes; RUL-UBP ECT: 8.8±5.8 minutes; Cohens d = 0.41), and CUAMI-SF consistency score (FEAST: 69.2±14.2%; RUL-UBP ECT: 63.9±9.9%; Cohens d = 0.43); findings that failed to meet statistical significance. FEAST exerts similar efficacy relative to an optimal form of conventional ECT and may have milder cognitive side effects. A blinded, randomized, non-inferiority trial is needed.

Objective: Electroconvulsive therapy (ECT) is the most rapid and effective antidepressant treatment but with concerns about cognitive adverse effects. A new form of ECT, focal electrically administered seizure therapy (FEAST), was designed to increase the focality of stimulation and better match stimulus parameters with neurophysiology. We recently reported on the safety and feasibility of FEAST in a cohort (n = 17) of depressed patients. We now report on the safety, feasibility, preliminary efficacy, and cognitive effects of FEAST in a new cohort. Methods: Open-label FEAST was administered to 20 depressed adults (6 men; 3 with bipolar disorder; age 49.1 ± 10.6 years). Clinical and cognitive assessments were obtained at baseline and end of course. Time to orientation recovery was assessed at each treatment. Nonresponders switched to conventional ECT. Results: Participants tolerated the treatment well with no dropouts. Five patients (25%) transitioned from FEAST to conventional ECT due to inadequate response. After FEAST (mean, 9.3 ± 3.5 sessions; range, 4–14), there was a 58.1% ± 36.0% improvement in Hamilton Rating Scale for Depression scores compared with that in the baseline (P < 0.0001); 13 (65%) of 20 patients met response criteria, and 11 (55%) of 20 met remission criteria. Patients achieved reorientation (4 of 5 items) in 4.4 ± 3.0 minutes (median, 4.5 minutes), timed from eyes opening. There was no deterioration in neuropsychological measures. Conclusions: These findings provide further support for the safety and efficacy of FEAST. The remission and response rates were in the range found using conventional ECT, and the time to reorientation may be quicker. However, without a randomized comparison group, conclusions are tentative.

An increasing proportion of the world has legalized cannabis for medicinal or recreational use. The legalization trend appears to be continuing. These changes in the legislative landscape may have important health, treatment, and research implications. This review discusses public health outcomes that may be impacted by increases in cannabis availability and use. It additionally considers potential research and treatment priorities in the face of widespread cannabis legalization.