lignans and Substance-Related-Disorders

Magnolia bark contains magnolol, metabolized to tetrahydromagnolol and honokiol, with both GABA-ergic/cannabimimetic activities, hence of possible attraction to vulnerable individuals/recreational misusers.. A literature review, assessment of related anecdotal online Magnolia misuse's reports and an overview of Magnolia products' online acquisition possibilities has been here described.. No peer-reviewed papers about Magnolia abuse/misuse/dependence/addiction were identified. Conversely, from a range of websites emerged potentially 3 groups of Magnolia misusers: (a) subjects with a psychiatric history already treated with benzodiazepines, being attracted to Magnolia bark as a "natural sedative"; (b) polydrug misusers, ingesting Magnolia with a range of other herbs/plants, attracted by the GABA-ergic/cannabimimetic activities; (c) subjects naive to the misusing drugs' scenario, perceiving Magnolia as a natural dietary supplement/weight-control compound.. To the best of our knowledge, this is the first paper commenting on the possible Magnolia derivatives' potential of misuse. Magnolia's recent increase in popularity, mainly as a sedative, may be arguably due to its peculiar pharmacological properties/acceptable affordability levels/virtually worldwide favorable legal status and customers' attraction to a product being perceived as "natural" and hence somehow "safe." Future/potent/synthetic magnolol and honokiol structural analogues could however contribute to increasing the number of synthetic GABA-ergic/cannabimimetic misusing compounds.

Topics: Biphenyl Compounds; Humans; Lignans; Magnolia; Plant Bark; Plant Extracts; Substance-Related Disorders

Use of the elevated plus-maze experiment and activity and traction tests in mice have revealed that seven daily treatments with 0.2 mg kg(-1) and higher doses of honokiol, a neolignane derivative extracted from Magnolia bark, had an anxiolytic effect without change in motor activity or muscle tone. Diazepam, 1 mg kg(-1), had the same anxiolytic potential as 0.2 mg kg(-1) honokiol but induced muscle relaxation. The aim of this study was to determine whether honokiol had diazepam-like side-effects. Mice treated with 1-10 mg kg(-1) diazepam, but not those treated with 0.1-2 mg kg(-1) honokiol, for 12 days showed withdrawal symptoms characterized by hyperactivity and running-fit when they were challenge-administered intraperitoneal flumazenil (10 mg kg(-1)) 24 h after the last treatment with diazepam. Oral diazepam (0.5-2 mg kg(-1), 10 min before) dose-dependently prolonged hexobarbital (100 mg kg(-1), i.p.)-induced sleeping, disrupted learning and memory, and inhibited (+)-bicuculline (40 mg kg(-1), i.p.)-induced death. Honokiol (0.2-20 mg kg(-1), p.o., 3 h before) had no such effects. The prolongation by diazepam (1 mg kg(-1)) of hexobarbital-induced sleeping was not modified by honokiol (0.2-20 mg kg(-1)). These results suggest that honokiol is less likely than diazepam to induce physical dependence, central depression and amnesia at doses eliciting the anxiolytic effect. It is also considered that honokiol might have no therapeutic effect in the treatment of convulsion.

Topics: Animals; Anti-Anxiety Agents; Behavior, Animal; Bicuculline; Biphenyl Compounds; Diazepam; Hexobarbital; Learning; Lignans; Male; Memory; Mice; Mice, Inbred BALB C; Sleep; Substance-Related Disorders