Oct 28 D&B

Cannabis and Drug Reinforcement

Introduction

  • Review of previous lectures on cannabis and neurochemical actions of THC.

  • Discussion of THC antagonist rimonabant and its past use in treatment.

  • Introduction to the concept of assessing rewarding effects of drugs through the operant self-administration paradigm.

Operant Self-Administration Paradigm

Importance in Drug Addiction Research

  • Used to identify which drugs are reinforcing and understand the neurochemical systems involved.

  • Ethical constraints limit testing on humans, necessitating the use of animal models, primarily rodents (rats and monkeys).

Description of the Procedure

  • hungry rat in a box with a lever to press for food as a reinforcement example.

  • Extension to drug reinforcement: animals press the lever for drug delivery.

  • Saline acts as a control; absence of lever pressing for saline indicates that the drug provides a reinforcing effect.

Key Findings from THC Studies

Dose-Response Relationships

  • Different doses of THC tested on monkeys to determine reinforcing effects:

    • 10 micrograms: not reinforcing.

    • 20 micrograms: reinforcing.

    • 40 micrograms: more reinforcing.

    • 80 micrograms: less reinforcing due to possible adverse effects.

Extinction and Reinstatement

  • Extinction: When THC was replaced with saline, bar pressing decreased, indicating a loss of reinforcement.

  • Reinstatement Studies: Reintroducing THC or the associated cue rekindled bar pressing, confirming its reinforcing properties.

Interaction with THC Antagonists

  • Administration of rimonabant blocks THC effects, reducing bar pressing behavior in the self-administration paradigm.

  • Potential therapeutic use of rimonabant noted, despite its adverse psychiatric effects.

Reinforcement of Other Drugs

Alcohol, Nicotine, and Stimulants

  • Alcohol: Animals can self-administer alcohol through liquid access or mist; reinforcing.

  • Nicotine: Strongly reinforcing, with dose-response similarities to THC.

  • Stimulants (Cocaine, Amphetamine): High reinforcing values; distinct binge-like consumption behavior.

Caffeine and Hallucinogens

  • Caffeine: Animals do not self-administer, indicating a difference in reinforcing qualities compared to humans.

  • Hallucinogens: Generally, animals do not self-administer traditional hallucinogens like LSD or psilocybin but may show some response to others like PCP.

Tolerance and Dependence of THC

  • THC produces tolerance to its effects; chronic users show decreased effects over time with consistent use.

  • Withdrawal symptoms observed in laboratory settings include wet dog shakes, restlessness, weight loss, and internal unrest. Symptoms generally resolve within 7 to 10 days.

Comparative Withdrawal Symptoms

  • Cannabis vs Tobacco: Symptoms largely overlap except for variations in appetite response.

    • Cannabis withdrawal leads to decreased appetite; tobacco withdrawal promotes increased appetite.

Treatment and Disorders

  • Estimated 30% of marijuana users may develop a use disorder, with typical clients being young and male.

  • No specific pharmacological treatments for marijuana use disorder currently exist; treatment approaches are similar to those for other substance use disorders.

  • Relapse rates post-treatment are high, with a significant portion of individuals returning to use shortly after treatment.

Synthetic Cannabinoids

  • Synthetic cannabinoids developed for medical purposes show higher potency and increased risk of adverse reactions compared to THC.

  • Potent synthetic cannabinoids have led to emergency room visits and health advisories due to their dangerous effects.

Conclusion

  • Summary of drug reinforcement studies and their implications for understanding cannabis and similar substances.

  • Upcoming quiz information noted, with an examination of tobacco scheduled for the next class.