The M/A potential of bupropion, most commonly via intranasal administration, is now broadly recognized based on several case reports describing desired effects that include a euphoric high and a stimulating “buzz” similar to that of cocaine or methamphetamine but less intense.29-36 Among recreational users, bupropion tablets are referred to as “welbys,” “wellies,” “dubs,” or “barnies.”37 Media coverage of a 2013 outbreak of bupropion M/A in Toronto detailed administration by snorting, smoking, and injection, and described bupropion as “poor man’s cocaine.”38 Between 2003 and 2016, 2,232 cases of bupropion misuse/abuse/dependence adverse drug reactions were reported to the European Monitoring Agency.37 A review of intentional bupropion M/A reported to US Poison Control Centers between 2000 to 2013 found 975 such cases, with the yearly number tripling between 2000 and 2012.39 In this sample, nearly half (45%) of the users were age 13 to 19, and 76% of cases involved oral ingestion. In addition to bupropion M/A among younger people, individuals who misuse bupropion often include those with existing SUDs but limited access to illicit stimulants and those trying to evade detection by urine toxicology screening.33 For example, widespread use and diversion has been well documented within correctional settings, and as a result, many facilities have removed bupropion from their formularies.21,28,33,34,40
Beyond desired effects, the most common adverse events associated with bupropion M/A are listed in Table 2,28,30,32-34,36,39 along with their incidence based on cases brought to the attention of US Poison Control Centers.39 With relatively little evidence of a significant bupropion withdrawal syndrome,37 the argument in favor of modeling bupropion as a truly addictive drug is limited to anecdotal reports of cravings and compulsive self-administration35 and pro-dopaminergic activity (reuptake inhibition) that might provide a mechanism for potential rewarding and reinforcing effects.40 While early preclinical studies of bupropion failed to provide evidence of amphetamine-like abuse potential,41,42 non-oral administration in amounts well beyond therapeutic dosing could account for euphoric effects and a greater risk of psychological dependence and addiction.21,28,40
Bupropion also has an FDA indication as an aid to smoking cessation treatment, and the medication demonstrated early promise in the pharmacologic treatment of psychostimulant use disorders, with reported improvements in cravings and other SUD outcomes.43-45 However, subsequent randomized controlled trials (RCTs) failed to demonstrate a clear therapeutic role for bupropion in the treatment of cocaine46,47 and methamphetamine use disorders (although some secondary analyses suggest possible therapeutic effects among non-daily stimulant users who are able to maintain good adherence with bupropion).48-51 Given these overall discouraging results, the additive seizure risk of bupropion use with concomitant psychostimulant use, and the potential for M/A and diversion of bupropion (particularly among those with existing SUDs), the use of bupropion for the off-label treatment of stimulant use disorders is not advised.
As dopamine antagonists, antipsychotics are typically considered to have low potential for rewarding or reinforcing effects. Indeed, misuse of antipsychotics was a rarity in the first-generation era, with only a few published reports of haloperidol M/A within a small cluster of naïve young people who developed acute EPS,52 and a report of diversion in a prison with the “sadistic” intent of inflicting dystonic reactions on others.53 A more recent report described 2additional cases of M/A involving haloperidol and trifluoperazine.54 Some authors have described occasional drug-seeking behavior for low-potency D2 blockers such as chlorpromazine, presumably based on their M/A as anticholinergic medications.55
The potential for antipsychotic M/A has gained wider recognition since the advent of the SGAs. Three cases of prescription olanzapine M/A have been published to date. One involved a man who malingered manic symptoms to obtain olanzapine, taking ≥40 mg at a time (beyond his prescribed dose of 20 mg twice daily) to get a “buzz,” and combining it with alcohol and benzodiazepines for additive effects or to “come down” from cocaine.56 This patient noted that olanzapine was “a popular drug at parties” and was bought, sold, or traded among users, and occasionally administered intravenously. Two other cases described women who self-administered olanzapine, 40 to 50 mg/d, for euphoric and anxiolytic effects.57,58 James et al59 detailed a sample of 28 adults who reported “non-medical use” of olanzapine for anxiolytic effects, as a sleep aid, or to “escape from worries.”
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