Slides+cannabis+Psychopharm

CANNABIS STudy Notes

INTRODUCTION

• Session focused on the following key topics:

  • The racism of marijuana-related arrests

  • The efficacy of CBD found in grocery stores, perceived as likely a placebo

  • Differences between indica and sativa cannabis strains

MARIJUANA DEFINITION

• Marijuana is derived from the cannabis plant, specifically Cannabis sativa.

• It is a mix of dried leaves and flowering tops.

• Common methods of consumption include:

  • Smoking (pipes, bongs, rolled cigarettes known as joints)

  • Vaping

  • Incorporation into edibles and drinks

• The major psychoactive compound in marijuana is Δ9-tetrahydrocannabinol (THC).

• Reported effects at low doses include:

  • Euphoria

  • Disinhibition

  • Relaxation

  • Altered sensations and experience of time

  • Increased appetite

  • Increased laughter

HISTORY OF CANNABIS

• 8000 BCE: First evidence of hemp fiber use in China.

• 2000 BCE: Evidence of medical use in China, India, and the Middle East.

• 1800: Napoleon's soldiers brought cannabis back from Egypt.

• 1900: Marijuana smoking likely entered the U.S. from Mexican and Caribbean immigrants.

• 1937: Introduction of the Marijuana Tax Act which regulated cannabis use.

MARIJUANA POSSESSION ARRESTS

• There are extreme racial disparities in marijuana-related arrests, persisting even in states where it is legalized or decriminalized:

  • Black individuals are 3.6 times more likely to be arrested compared to white individuals, despite similar usage rates.

  • Mention of a video segment at 8:49 discussing these disparities.

PHARMACOLOGY OF MARIJUANA

• When smoked, THC is easily absorbed by the lungs, resulting in a rapid rise in blood plasma levels.

• Oral consumption leads to poor absorption of THC with low and variable plasma concentrations due to first-pass metabolism.

• Elimination of THC metabolites occurs through feces and urine, with a slow process owing to storage in fat tissue.

• THC-COOH can be detected in urine for up to 2 weeks.

CANNABIDIOL (CBD)

• CBD shares a similar structure to THC but does not produce intoxicating or dependence effects.

• Notable for its ability to reduce seizures in specific rare genetic disorders, particularly offered as Epidiolex, which contains 99% CBD.

• FDA approval granted in 2018.

• Discussions are ongoing about its role in therapy for autism, but skepticism remains about the efficacy of over-the-counter CBD products.

• Video segment at 16:17 explores CBD.

MECHANISMS OF CANNABIS ACTION

• Activation of cannabinoid receptors induces a powerful inhibitory effect on neurotransmitter (NT) release.

• CB1 receptors were discovered in 1988 and are expressed in many brain areas, including:

  • Basal ganglia

  • Cerebellum

  • Hippocampus

  • Cortex

• CB2 receptors play a role in the immune system and brain function.

CB1 Receptor Function

• THC acts as a partial agonist at CB1 receptors, resulting in a lower peak effect compared to other full agonists.

• In research on mice, THC’s effects included:

  • Reduced locomotor activity

  • Hypothermia

  • Catalepsy

  • Hypoalgesia

• Biphasic effects on anxiety behavior:

  • At low doses: anxiolytic effect due to inhibition of glutamate release

  • At high doses: anxiogenic effect due to inhibition of GABA release

CBD MECHANISMS

• CBD is not a cannabinoid receptor agonist; instead, it acts as a negative allosteric modulator of CB1 receptors.

• CBD inhibits the breakdown of endogenous cannabinoids, thereby enhancing the activity of the endocannabinoid system.

ENDOCANNABINOIDS

• Endocannabinoids are receptor agonists produced within the body.

• Two notable endocannabinoids identified are:

  • Anandamide: a partial agonist at CB1 with low efficacy at CB2.

  • 2-arachidonoylglycerol (2-AG): a full agonist at both CB1 and CB2.

• Endocannabinoids are not stored in vesicles due to their lipid nature; their release is triggered by a rise in intracellular calcium levels.

• Metabolic involvement primarily through cyclooxygenase-2 (COX-2), which plays a minor role in inflammatory processes.

ENDOCANNABINOID SIGNALING

• Signaling is primarily retrograde, meaning it travels from postsynaptic to presynaptic neurons, usually involving 2-AG.

• Anandamide typically mediates non-retrograde signaling, interacting with CB1 or TRPV1 receptors.

• TRPV1 has a key role in heat pain sensation via capsaicin at neuron-astrocyte interfaces, activating receptors in astrocytes and prompting glutamate release from glial cells.

FUNCTION OF ENDOCANNABINOIDS

• Critical roles include diverse physiological functions:

  • Mood regulation: anxiety, fear, and stress reactions.

  • Facilitating the extinction of learned fear, potentially implicating dysfunction in PTSD.

  • Regulation of eating behaviors including hunger and energy metabolism.

  • Rimonabant (Accomplia): a synthetic CB1 antagonist that reduces food consumption.

  • Pain perception modulation: cannabinoids can potentiate opioid-induced analgesia and decrease opioid-related tolerance, thereby reducing the risk of opioid addiction.

  • The roles of THC and CBD in medical marijuana uses were emphasized in video segments at 7:00 and 3:51 respectively.

ACUTE EFFECTS OF CANNABIS

• Mediated via CB1 receptors, acute effects can be categorized into four stages:

  • Buzz: brief period involving lightheadedness and slight dizziness

  • High: characterized by euphoria, exhilaration, disinhibition, and laughter

  • Stoned: occurs at higher doses with calmness, relaxation, dream-like perceptions, and altered time perception

  • Come-down: a gradual cessation of effects

• Physical responses to cannabis use may include:

  • Increased heart rate and blood pressure

  • Heightened hunger

• Adverse reactions at high doses include:

  • Increased anxiety

  • Transient psychotic symptoms

  • Paranoia

  • Violent behavior, particularly in first-time users

• Acute toxic reactions can occur from extreme doses, leading to:

  • Tachycardia

  • Gastrointestinal symptoms