Episode 92: The Effects Of Cannabis (Marijuana) On The Brain & Body | Huberman Lab

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Key Takeaways

  • Nicotinic receptors and cannabinoid receptors are not in the brain for smoking tobacco or marijuana; they are endogenous receptors that support specific functions (such as acetylcholine) when appropriate
  • Cannabis dependence: when smoked or ingested, THC and CBD bind to cannabinoid receptors and tap into endogenous receptors with much more potency – your endogenous receptors are outcompeted  
  • Sativa strains increase mood, alertness, and focus of the prefrontal cortex while decreasing stress and threat detection in the amygdala – this combination allows people to enter narrowed focus  
  • Indica strains reduce the activity of the prefrontal cortex and induce relaxation and sedative effects but also lead to profound defects in short-term memory because it reduces the activity of the hippocampus
  • There are no predictors of what your reaction will be to a given strain (e.g., whether you experience relaxation or paranoia)
  • “Cannabis increases creativity but through changes in personality that tap into the creative process, rather than directly impacting the neural circuits that, for instance, ‘turn on’ creativity.” – Dr. Andrew Huberman
  • Smoking cannabis increases prolactin levels (especially in those who smoke more than twice per week); dopamine and prolactin are mutually inhibitory – this is important in sexual arousal which will be suppressed if prolactin is elevated with cannabis use
  • Fertility: THC (not CBD) is inhibitory for gonadotropin-releasing hormone which ultimately reduces testosterone in men, ovarian health in women
  • “Cannabis use itself makes people 4x likelier to develop a chronic, major depression.” – Dr. Andrew Huberman
  • Chronic cannabis is not safe for the developing brain and body because of thinning of gray matter that occurs – risks include depression, anxiety, psychotic events, inability to balance mood
  • The more potent the THC concentration, the higher the likelihood of developing a major anxiety disorder or psychotic episode later in life

Introduction

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)

Overview Of Cannabis Plant

  • 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

Understanding Brain Receptors

  • 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

  • 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)

What Happens When You Ingest Cannabis?

  • 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

Cannabis & Creativity

  • 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

How Cannabis Use Changes Speech

  • 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

Cannabis Use, Libido & Effects On Hormones

  • 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

Negative Health Effects Of Cannabis Use

  • 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

Positive Uses Of Cannabis In Adults

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

Resources

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