LEC 14: Substance use disorders and cannabis

What is reward?

Refers to stimuli that are in some way desirable or positive and can affect behaviour

The Mesocorticolimbic Dopamine system

• aka the Reward System

• dopamine is the main neurotransmitter used in this system

• neurons in the ventral tegmental area project axons to regions in the limbic system and cortex:

  • hippocampus

  • nucleus accumbens

  • prefrontal cortex

• when a rewarding stimulus is detected, neurons in the VTA are activated and release dopamine

• addictive drugs lead to suprahysiological dopamine, a dopamine release that is much larger than normal with naturally occurring rewards

Addiction

a syndrome at the center of which is loss of control over a reward-seeking behaviour

Diagnostic criteria for substance use disorders

• tolerance

• withdrawal

• craving

• using in spite of adverse consequences

Symptoms and effects of drug withdrawal

Symptoms: muscle aches, anxiety attacks, nausea, convulsions

Effects:

1. The brain normally exists in a state of drug-free homeostasis

2. Taking drugs leads to an imbalance

3. Compensatory adaptations attempt to restore homeostasis

4. Withdrawal: quitting drugs leads to an imbalance in the opposite direction

Prevalence of substance use disorders

Around 4% of population will receive a diagnosis of a substance use disorder

The endocannabinoid system

• this system is activated in times of stress; helps regulate/return to baseline

• endogenous ligands: anadamide (AEA) and 2-arachidonoylglycerol (2-AG)

• two main receptors: CB1 (brain) and CB2 (immune system)

• anandamide and THC bind to CB1

• 2-AG and CBD bind to both CB1 and CB2

Cannabinoid action on the brain

• hypothalamus: appetite

• cerebral cortex: higher cognitive function

• hippocampus: learning, memory, stress

• cerebellum: movement

How endocannabinoids work, and how THC works

Endocannabinoids:

• CB1 receptors are located presynaptically on axon terminals

• AEA and 2-AG are retrograde messengers, they carry information in the opposite direction from normal (i.e. postsynaptic to presynaptic)

• Function: to inhibit/regulate the activity of several neurotransmitters after stress

THC:

• THC mimics the shape of AEA and works by exploiting this mechanism

Cannabis and psychosis

Frequent use of high-THC cannabis is associated with an increased risk of developing psychotic symptoms, especially young males who use (near) daily before the age of 16 AND have a variation in the COMPT gene

Harms associated with chronic cannabis use

• studies suggest frequent use of high-THC cannabis is associated with an increased risk of developing depression

• heavy or frequent cannabis use, especially in younger populations, may be linked to an increased risk of suicidal thoughts, attempts, and behaviours