Cannabiss Impact on the Brain & Body | Huberman Lab Episode 92 

Dr. Andrew Huberman, Ph.D. is a Professor of Neurobiology and Ophthalmology at Stanford University School of Medicine. His lab focuses on neural regeneration, neuroplasticity, and brain states such as stress, focus, fear, and optimal performance.

In this episode of the Huberman Lab podcast, Andrew Huberman takes a deep dive into all things cannabis: biological mechanisms underlying its effects, medical applications, impact on body systems, adverse health consequences, and much more. Host: Andrew Huberman (@hubermanlab)

Cannabis contains over 70 psychoactive compounds and 400 biologically active compounds, most notably THC (tetrahydrocannabinol), CBD (cannabinoid), and CDN (cannabinol) THC is largely responsible for the psychoactive effects of cannabis (changes in mood, body state, etc.)

CBD has profound effects on the brain and body but without perception of altered mood – CBD doesn’t “get you high” Cannabis plants come in different genetic strains naturally and via hybridization

Sativa strain : creates a head “high” and acts as a stimulant – invigorating, alert, heightened sense of creativity and focus, less susceptible to pain; can be consumed by smoking, edible, sublingual

Indica strain : creates a more full body relaxation, sedative effect; can be consumed by smoking, edible, sublingual Ruderalis strain : not often consumed for medicinal or recreational purposes

Hybrid strains combine sativa and indica strains to give rise to nuanced brain and body effects Each strain is further be classified into Type 1 (THC dominant), Type 2 (equal ratios THC:CBD), and Type 3 (CBD dominant) strains based on the ratio of THC to CBD

Nicotinic receptors are naturally occurring in the brain and body, binding acetylcholine Nicotine from tobacco binds to the nicotinic receptors which have greater affinity and create intense focus not naturally produced in the body

Similarly, we have cannabinoid receptors in cells of the brain and body that cause biological effects on mood, hunger, etc. when endogenous chemical binds

Marijuana binds to cannabinoid receptors in the brain and body with much greater potency than endogenous cannabinoids If you take synthetic estrogen or testosterone, they have super-physiologic effects

Endogenous cannabinoids are released from neurons Unlike most neurotransmitters, endogenous cannabinoids are released from post-synaptic neurons

Endogenous cannabinoids change the probability (both up and down) that a neuron will release a neurotransmitter – it allows for adjustment of communication between neurons

There are two kinds of endogenous cannabinoid receptors : (1) CB1 is largely located in the nervous system – brain and spinal cord; (2) CB2 is located throughout the body

Cannabis potently binds CB1 receptor: the binding is so strong, they out-compete endogenous cannabinoid system Endogenous CB1 and CB2 receptors are present throughout development, starting at fetal development

CB1 receptor activation is critical for every aspect of brain wiring and development You should not use cannabis during pregnancy or breastfeeding – CBD is no safer (yet about 15% of pregnant mothers admit to cannabis use during pregnancy)

Cannabis enters the bloodstream within 30 seconds (extremely fast delivery) Within 30-60 minutes cannabis reaches its peak effects which lasts 3-4 hours generally (but it depends on the body and frequency of use)

Cannabis cells are highly lipophilic: they bind to the fatty membrane around neurons and get into most cells and remain there for a long time Cannabis will be detectable in the system for around 80 days because of its lipophilic nature

Sativa: stimulant, mood elevation, energetic, head high, narrowed sense of focus, increase CB1 activation, an overall reduction in stress – and at the same time – quieting other circuitry

Indica: relaxing, sedative effects, shuts down threat detectors in the brain, binds to CB1 receptors Whatever effect you feel (alert, anxious, paranoid, calm, etc.) with a particular strain, you will experience it every time – your reaction doesn’t change

Deficits in memory are due to reductions in the electrical activity of the hippocampus which is responsible for short-term memory People who use cannabis tend to be less physically active because basal ganglia and cerebellum are suppressed

Reddening of the eyes and dryness of mouth is due to reductions in saliva because of CB1 and CB2 receptors in eyes and mouth

“Munchies” happen because of signaling of the hypothalamus to the gut which activates neurons and triggers: (1) preoccupation with anticipation and taste of food; (2) narrowed focus on food There are some anti-pain effects from CB1 effects

Note: most studies don’t distinguish between indica and sativa strains Aside from those who just like being high, people use marijuana to achieve a certain state (such as creativity)

Convergent thinking: taking loose ideas and synthesizing them into a specific framework or coherent idea(s) Divergent thinking: brainstorming, exploring ideas Dopamine is closely related to convergent and divergent thinking and creativity

In professions where there’s a lot of creativity required (such as artist, musician) there tends to be a lot of manic depression When dopamine is high, divergent thinking is more frequent, and convergent thinking is low – until a threshold is passed and divergent thinking sinks

Creativity is a process, not an event There is evidence cannabis enhances creativity (by driving dopamine and divergent thinking) but it could be because cannabis users are more open to novel thinking and experiences

Cannabis may unlock a willingness to explore different options by reducing anxiety

Both sativa and indica strains impact basal ganglia and CB1 which disrupts neural circuitry – speech is the movement of the mouth People who smoke sativas tend to be more talkative

Effects of chronic use of cannabis on speech: (1) change in vocal effort & intensity; (2) changes in pronunciation of words and emphasis on particular words in a sentence Cannabis users may read sentences with less intonation and annunciation in voice

Around 6-9% of people have hypoactive sexual desire and activity disorder (reduced libido) Nucleus accumbens and dopamine are particularly vital in sex pathways

Effects of cannabis on sex are highly divergent: some individuals experience increased libido, and some experience suppressed libido Prolactin and dopamine are opposing – when dopamine is high, prolactin is low, and vice versa

For people who experience elevated prolactin levels when using marijuana, areas of the brain responsible for sexual arousal were not activated; for people who experience sexual arousal when using cannabis, prolactin is not elevated

Levels of baseline prolactin do not predict whether you will experience elevated prolactin when using cannabis Smoking marijuana more than twice per week increases prolactin levels

It seems edible marijuana does not have the same effect on libido and prolactin but the research is not extensive enough to draw definitive conclusions

Chronic smoking (more than 2x per week) does appear to reduce testosterone significantly and elevate aromatase enzymes (enzymes which convert testosterone into estrogen) – some men experience gynecomastia with chronic use Chronic cannabis does seem to impair sperm motility

Cannabis increases cortisol in some and reduces it in others THC (not CBD) is inhibitory for gonadotropin-releasing hormone which ultimately reduces testosterone in men, ovarian health in women

The process of smoking or vaping anything severely impairs the function of endothelial cells that make up the brain and body Just because marijuana is legal in many places, doesn’t mean it’s safe for everyone

Levels of anxiety and depression increase over 12 months in chronic users (more than 2x per week) of marijuana

Some of the highest chronic use of cannabis is among youth 16-24 (working or students) – this is concerning because it leads to a higher likelihood of developing depression, anxiety, or psychosis later in life because the brain is still developing

In youth who start using marijuana at 12 or 14, the risk of the psychotic episode is greatly increased because of thinning of gray matter (involved in planning & executing plans, and organizing life)

Some (not all) recovery of brain function can be restored: focus on behaviors that increase brain health (future episode coming soon) like cardiovascular exercise

Cancer: increase appetite, reduce nausea Glaucoma: reduce intraocular pressure Pain reduction

Articles Inspired by Mary Jane? Mechanisms underlying enhanced creativity in cannabis users ( Consciousness and Cognition ) Adults with a history of recreational cannabis use have altered speech production ( Drug and Alcohol Dependence ) Individual prolactin reactivity modulates response of nucleus accumbens to erotic stimuli during acute cannabis intoxication: an fMRI pilot study ( Psychopharmacology ) Bayesian causal network modeling suggests adolescent cannabis use accelerates prefrontal cortical thinning ( Translational Psychiatry ) Association of cannabis potency with mental ill health and addiction: a systematic review ( The Lancet Psychiatry )

Other Links Huberman Lab Premium NSDR Protocol with Dr. Huberman on YouTube