Cannabinoids

Behavioral Mechanism of Action

Cannabis and its active ingredient Δ9-THC have behavioral effects that intersect with two drug classes: sedative hypnotics and psychedelics. Sedative-hypnotic drugs disinhibit behavior (i.e., individuals show a release of inhibitions in situations where normally they might be socially constrained). Alcohol is widely used as a social lubricant to promote conversation and social interaction. The disinhibition associated with alcohol is often mistaken for a psychostimulant effect, and alcohol is often labeled as a stimulant at lower doses. The disinhibition produced by cannabis is more cognitive or perceptual, with a pronounced decrease in motivation to exert energy, thus limiting any actual disinhibited behavior that would resemble the stimulant-like effects of alcohol. The increased psychedelic-like perceptual effects, decreased motivation, and impaired cognitive function associated with high doses of Δ9-THC lead to a unique behavioral mechanism of action that presumably exaggerates the normal actions mediated by endogenous cannabinoids.

Box 8.8

CASE HISTORY

A 20-year-old male driver was checked during a general road traffic control. The police noted: “vestibular disorder, disturbance of fine motor skills, enlarged pupils, and blunt mood.” A blood sample was taken 80 min later with the following notes being made by the physician: “finger-to-finger test doubtful, obviously enlarged pupils, and delayed reaction of the pupils to light.”

Toxicological results [for synthetic cannabinoids with CB1 receptor agonist activity]:

  • JWH-019 1.7 ng/ml
  • JWH-122 7.6 ng/ml
  • JWH-210 4.4 ng/ml
  • AM-2201 0.31 ng/ml

From: Musshoff F, Madea B, Kernbach-Wighton G, Bicker W, Kneisel S, Hutter M, Auwärter V. Driving under the influence of synthetic cannabinoids (“Spice”): a case series. International Journal of Legal Medicine, 2013, (128), 59–64.

TABLE 8.14

Spice-Induced Adverse Clinical Effects

Central effects

Psychosis

 

Seizures

 

Anxiety

 

Agitation

 

Irritability

 

Memory changes

 

Sedation

 

Confusion

Cardiovascular effects

Tachycardia

 

Tachyarrhythmia

 

Cardiotoxicity

 

Chest pain

Gastrointestinal effects

Nausea

 

Vomiting

Other effects

Somnolence

 

Dilated pupils

 

Brisk reflexes

 

Emesis

 

Appetite changes

 

Tolerance

 

Withdrawal

 

Drug dependence

From: Seely KA, Lapoint J, Moran JH, Fattore L. Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids. Progress in Neuropsychopharmacology and Biological Psychiatry, 2012, (39), 234–243

Endogenous cannabinoids (see below) may play a functional role in the brain to temper excessive arousal and excessive cognitive function but increase the response to novelty, thus increasing perceptual function and facilitating hedonic processes. Marijuana may induce variability in information processing by higher brain structures that involve executive function, leading to the retardation of habituation of classical reinforcers and inducing novel experiences. Cannabinoids may also amplify the hedonic aspects of eating. Thus, the behavioral mechanism of action of cannabinoids may involve perceptual disinhibition of both external and internal cues/states without motivational disinhibition. This perceptual disinhibition can be pleasant in an appropriate external context with positive valence, ranging from external sensory modalities (visual, auditory, and tactile) to the taste modality (sweet or particularly palatable food), or can be unpleasant in situations with negative emotional valence.

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