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

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