Thursday, December 30, 2004

Endocannabinoids, buspirone (Buspar), and behavioral disorders in children with ADHD, PDD, EBD (explosive child)?

Haller J, Varga B, Ledent C, Barna I, Freund TF. Context-dependent effects of CB1 cannabinoid gene disruption on anxiety-like and social behaviour in mice. Eur J Neurosci. 2004 Apr;19(7):1906-12.

This is a mouse study:
CB1 gene disruption promoted aggressive behaviour in the home-cage, whereas it inhibited social behaviour in the unfamiliar cage. Thus, the anxiogenic-like effect was restricted to the more stressful unfamiliar environment. These data suggest that the effects of CB1 gene disruption were context and not behaviour specific. Novelty stress resulted in higher ACTH levels in CB1-KOs than in WTs, which suggests that context dependency occurred in conjunction with an altered HPA axis function. The present data at least partly explain contrasting effects of cannabinoids in different contexts as well as in different species and strains that show differential stress responses and coping strategies.

The endocannabinoids are a relatively recently identified set of neurotransmitters. They affect appetite, diet, social behavior, anxiety, aggression, sleep, memory, and learning. Most of our knowledge comes from the effects of the plant cannabinoids (marijuana, etc).

Naturally there is great therapeutic interest in the endocannabinoids. If we could influence their activity in a safe manner we might have new ways to treat disorders of anxiety, of aggression, and of diet (both anorexia and obesity).

Coincidentally, fairly recently there've been studies of using Buspar, a medication marketed as an anxiolytic (Buspar abolishes REM sleep -- a side-effect that I feel has been rather understudied), for marijuana withdrawal syndrome (aggression, anxiety).

Buspar has also been used in children with anxiety and behavioral disorders, including the group that gets labeled as "Emotional behavioral disorder/EBD", Pervasive Developmental Disorder (PDD), severe ADHD, and "exposive disorder".

Also, some of the behaviors of these children, including a peculiarly setting specifiic tendency to either anxiety/withdrawal or aggression, resembles marijuana withdrawal syndrome.

Lastly, book I've quite appreciated, written by an adult who'd suffered from severe ADHD/Explosive disorder, emphasized how severe his withdrawal syndrome was from marijuana, and provided anectdotal evidence that for children with ADHD marijuana is a particularly disruptive drug.

Given all of the above, it does not seem to be a great leap to a speculative relationship: Buspirone and endocannabinoids and "Explosive Disorder"/ADHD.

An interesting axis to explore. So I fired up and entered the search terms: endocannabinoid buspirone. Intriguingly that led to the article cited here, a mouse study that makes no mention anywhere (in the abstract) of buspirone). More mysteries of Google! The study does, however, note that Endocannabinoid CB1 disruption did produce a peculiar mouse behavior -- anxiety/withdrawal in unfamiliar settings, aggression/activity in familiar settings. Hmmm. That sounds interesting.

It will be very interesting over the next few years to see how the Buspar, endocannabinoid, CB1, ADHD, PDD, explosive child, EBD, CCBD (complex cognitive behavioral disorder) axis evolves. Look for some interesting work on children with EBD using PET scans and Buspar. We are probably five to ten years from well undestood therapies however -- even if this relationship holds up.

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