Dr. Matthew Hill: How Cannabis Impacts Health & the Potential Risks

08 Jul 2024 (5 months ago)

Cannabis and Its Effects

Cannabis, particularly THC, is the primary psychoactive compound responsible for the intoxicating effects of the plant.
Cannabis has a rich history of use across cultures for medicinal, spiritual, and recreational purposes.
The use of cannabis became popularized in the West during the 1960s and has since become widely used by a large population, including teenagers.
The psychoactive effects of cannabis include euphoria, altered perception, and changes in mood and behavior.
The mechanism by which cannabis affects time perception is not well understood but studies suggest it may alter the perception of time passing.
Cannabis can stimulate appetite, which is why it is sometimes used medically to treat cancer patients experiencing appetite loss.
The euphoric effects of cannabis are not directly caused by dopamine but may be related to the disinhibition of dopamine neurons by cannabinoids.

Endocannabinoids are molecules produced by the body that act on CB1 receptors and play a crucial role in maintaining homeostasis in the brain.
Endocannabinoids regulate the release of neurotransmitters, preventing runaway excitation or inhibition in neuronal circuits.
CB1 receptors are found on almost all neurons in the brain, except for dopamine neurons.
Anandamide and 2-arachidonoylglycerol (2-AG) are the two main endocannabinoids.
The endocannabinoid system is widely distributed throughout the brain, except in brainstem populations that regulate unconscious cardiac and respiratory function.
This difference in receptor localization is why cannabis overdoses are not fatal, unlike opiate overdoses which can depress neural activity in the brainstem and lead to respiratory depression.
The endocannabinoid system has both tonic and phasic capabilities, allowing for both steady release and spikes in activity.

Cannabinoid receptors are expressed in feeding circuits in the hypothalamus, and activation of these receptors can stimulate appetite and lead to the munchies.
Cannabinoids regulate inhibitory inputs around AGRP neurons, disinhibiting them and driving food-seeking behavior.
Cannabinoids also have a reward component, enhancing the response to sweet taste buds in the gustatory cortex and integrating with the reward circuitry.
The munchies involve both increased food-seeking and maintenance of eating, disrupting satiety detection or reward devaluation.
Experiments show that animals will reinitiate eating and work harder for food when under the influence of cannabis, even if they are satiated or the food has been devalued through pairing with a nauseant.
This suggests that cannabinoids lock in the reward value of food, preventing decay despite satiety, and can override satiety signals such as leptin.

AG1 is a nutritional supplement designed to provide foundational nutrition and support overall well-being, including mental and physical health.
It contains a combination of vitamins, minerals, probiotics, and adaptogens to help cope with stress.
Unlike many supplements that target specific outcomes, AG1 is formulated to support all aspects of well-being.

Boosting anandamide levels, another endocannabinoid, through drugs that inhibit its breakdown has shown promise in reducing stress and fear without psychoactive effects.
Research on drugs that elevate anandamide levels has demonstrated their potential in modulating pain, stress, and fear responses.
Ongoing research is exploring the therapeutic applications of drugs that boost anandamide levels in various clinical settings, such as PTSD and social anxiety disorder.

THC acts as a ligand, indiscriminately activating CB1 receptors throughout the brain, leading to the intoxicating effects of cannabis.
Unlike THC, endocannabinoids are released in a specific spatial and temporal manner, amplifying signaling at specific synapses.

The effects of cannabis on focus and memory are not well-studied, with anecdotal evidence suggesting both positive and negative effects.
Animal evidence suggests short-term memory deficits during cannabis intoxication, but there is limited evidence of long-term effects in humans who use cannabis regularly.
Regular cannabis users may develop tolerance or adapt to the effects of cannabis, reducing the impact on memory processing.
State-dependent learning can occur, where individuals who perform tasks while intoxicated may become proficient at those tasks under the influence.
Acute cannabis intoxication generally impairs memory processes, but the specific form of memory affected is not well-established.
There is no compelling evidence of long-term, permanent effects on cognitive function in individuals who use cannabis.

Cannabis potency has increased significantly over time, with commercial cannabis often containing 20-30% THC compared to 5% in the 1970s.
People tend to self-regulate their intake of cannabis to achieve similar blood THC levels, regardless of the potency of the cannabis.
Concentrates, which can have THC levels of up to 90-98%, can lead to higher blood THC levels and are more challenging to self-titrate.
Rodents also exhibit self-titration behavior when given access to different potency cannabis products, preferring medium potency products and taking fewer hits of high potency products.
The high THC content in modern cannabis, especially in concentrates, is a concern due to the potential for increased tolerance and harm.

Chronic cannabis users may exhibit some degree of tolerance, but it is not as profound as with other drugs like cocaine or alcohol.
High-potency extracts and concentrates can lead to more profound tolerance due to the inability to titrate the dose effectively.
Cannabis can be addictive or habit-forming, but it is important to distinguish between the two.
Cannabis use disorder is a real condition that can consume a person's life and lead to risky behaviors.
The conversion rate from cannabis use to developing a use disorder is estimated to be around 30% for those who use weekly.