Cannabinoid
Episodes
Dr. Rhonda Patrick makes her third appearance on the Joe Rogan Experience.
-
Brain Nutrition Exercise Alzheimer's Cholesterol Omega-3 Inflammation Depression Probiotics DNA Damage Stem Cells Serotonin Mental Health Cannabinoid CurcuminDr. Rhonda Patrick makes her third appearance on the Joe Rogan Experience.
Topic Pages
News & Publications
-
Cannabis use is prevalent among teens, whose brains are undergoing massive developmental changes. Evidence suggests that THC (tetrahydrocannabinol), the primary psychoactive ingredient in cannabis, has profound effects on the brain, impairing neurodevelopment. A recent study in mice found that adolescent cannabis use influences gene expression and neural connections, potentially altering the brain’s structure.
Researchers exposed adolescent male mice to THC and then analyzed changes in gene expression and brain cell structure within the cerebral cortex—a brain region responsible for memory, thinking, learning, reasoning, problem-solving, emotions, consciousness, and sensory functions. They also scanned the brains of more than 450 adolescent human males to compare the cerebral cortex thickness of those who tried cannabis before age 16 to those who did not.
They found that adolescent mice exposed to THC exhibited less dendritic branching and fewer neural spines, indicating a loss of complexity in brain cells. Similarly, human teens who used cannabis had thinner cortex regions. Further analysis linked these structural changes to genes involved in brain development, including processes like learning and memory.
These findings suggest that early cannabis exposure interferes with the normal development of brain structure, especially in areas critical for learning and emotional regulation. This interference likely occurs through effects on specific genes and brain cells responsible for building neural connections during adolescence.
Teens aren’t the only ones at risk for the harmful developmental effects of THC exposure—the compound can pass into breast milk, influencing an infant’s neurodevelopment. Learn more in this clip featuring Dr. Rhonda Patrick.
-
Cannabidiol restores the gut microbiome in cocaine users, weakening memory of the drug's reward, according to a study on mice. www.psypost.org
Cocaine affects nearly every organ system in the body, including the gastrointestinal system, drastically altering the gut microbiome. It also increases dopamine levels in the brain, creating a memory of the dopamine reward and strengthening the association between the drug and the pleasurable feelings it produces. A recent study in mice found that cannabidiol, a non-psychoactive compound in marijuana, restores the gut microbiome in cocaine users, reversing memory-associated cocaine addiction.
Researchers gave adult mice either cocaine + placebo or cocaine + cannabidiol. They collected fecal samples before and after the drug treatments to analyze changes in the gut microbiome.
They found that the mice that received cocaine + placebo developed a strong preference for environments where they received the drug that lasted even after its cessation, indicating they had a memory of the reward. These mice also experienced long-lasting reductions in their gut microbial diversity. However, the mice that received cocaine + cannabidiol showed a reduced preference for the cocaine-associated environment after drug cessation and exhibited greater gut microbial diversity, with more beneficial microbes and fewer harmful ones.
These findings suggest that cannabidiol reverses changes in the gut microbiome caused by cocaine and helps reduce the memory of cocaine’s rewarding effects. Beneficial activities like exercise and hard work also boost dopamine levels but without the massive peaks associated with cocaine use. Learn more in this clip featuring Dr. Andrew Huberman.
-
THC from a single use of cannabis accumulates in breast milk for up to 12 hours in breastfeeding women. news.wsu.edu
Breastfeeding is the biologically superior way to feed an infant. However, harmful substances in the mother’s blood can transfer to and accumulate in her breast milk. A recent study found that tetrahydrocannabinol (THC), the primary psychoactive ingredient in cannabis, accumulates in breast milk after a single use, persisting for several hours.
The study included 20 healthy young women who were breastfeeding their infants and used cannabis at least once weekly. Participants collected samples of their breast milk after abstaining from cannabis use for at least 12 hours and at several intervals over an eight- to 12-hour period after use.
Researchers found that participants' breast milk contained THC even after 12 hours of abstention. THC concentrations peaked about two hours after cannabis use; however, in some cases, concentrations peaked as early as half an hour after use. Concentrations were higher with multiple uses and remained elevated throughout the 12-hour study period. On average, infants received approximately 16.2 micrograms per kilogram of body weight of THC over 12 hours.
These findings suggest that THC accumulates in breast milk after a single use of cannabis. The effects of THC on the developing infant brain are unclear. However, research on rodents has identified lasting, mild effects on memory and learning following a single, extremely low dose of THC equivalent to 0.2 micrograms per kilogram in humans – far less than the average dose the infants in this study received. Other harmful compounds, including nicotine, caffeine, and heavy metals, can pass into breast milk, too. Learn more about breast milk and breastfeeding in our overview article.
-
Daily cannabis use more than doubles the chance of stroke among non-tobacco users, suggesting cannabis use alone could contribute to cardiovascular disease risk. www.ahajournals.org
Cannabis, commonly known as marijuana, is a plant used for its psychoactive properties and influences on perception, mood, and consciousness. People consume cannabis for both recreational and medicinal purposes, seeking relief from pain, anxiety, and other conditions. A recent study found that regular cannabis use increases the risk of cardiovascular disease, particularly among those who don’t use tobacco.
Researchers analyzed data collected from more than 434,000 adult participants who provided information about their cannabis use. They looked at how often participants used cannabis in the past month and whether they reported having coronary artery disease, a heart attack, or a stroke. They conducted a separate analysis for participants who didn’t use tobacco.
They found that daily cannabis users were about 16 percent more likely to have coronary heart disease, 25 percent more likely to experience a heart attack, and 42 percent more likely to have a stroke. When they combined all three heart-related issues, they found that daily cannabis users were 28 percent more likely to face any of them than non-users.
However, when they focused on participants who had never smoked tobacco and only used cannabis, the findings were even more striking. Daily cannabis users who had never used tobacco were 49 percent more likely to experience a heart attack and 116 percent more likely to have a stroke. When the researchers combined all three heart-related issues, they found that daily cannabis users who had never used tobacco were 77 percent more likely to face any of the cardiovascular conditions.
These findings suggest that daily cannabis use increases the risk of cardiovascular disease, especially among non-tobacco users, indicating that cannabis use alone could contribute to cardiovascular risk. Compounds in cannabis have profound effects on the human body and can even pass into breast milk, affecting breastfed infants. Learn more in this episode featuring Dr. Rhonda Patrick.
-
Cannabinoids promote bone fracture healing and relieve pain in mice. www.sciencedaily.com
Cannabinoids are bioactive compounds found in the Cannabis sativa plant – the source of hemp and marijuana. Evidence suggests they help treat addiction, prevent seizures in certain seizure disorders, and reduce inflammation. A new study in mice shows that cannabinoids relieve pain as effectively as non-steroidal anti-inflammatory drugs (NSAIDs) while also promoting bone fracture healing.
Researchers studied the effects of cannabidiol (CBD) and cannabigerol (CBG) on bone healing in mice that had experienced a fractured tibia (a lower leg bone). They injected the mice with cannabinoids (CBD or CBG) or NSAIDs (indomethacin or celecoxib) daily for four weeks and assessed the animals' pain throughout the study duration. At the end of the study, they examined the animals' tibias to assess healing.
They found that CBD and CBG helped manage pain in mice with bone fractures as effectively as NSAIDs. However, the cannabinoids also promoted fracture healing. In the early healing stage, they increased the number of periosteal bone progenitors (cells that later help form bone tissue). In the later healing phase, the cannabinoids accelerated the absorption of minerals to strengthen the new bone, making it functionally healthy.
These findings indicate that cannabinoids CBD and CBG may be useful alternatives to NSAIDs in an animal model of bone fracture. As their name suggests, NSAIDs block inflammation, an important early step in bone healing. Taking NSAIDs increases a person’s risk for many complications, including gastrointestinal bleeding and cardiovascular events, such as stroke or heart attack. NSAIDs also block some of the beneficial effects of exercise. Learn more in this episode featuring Dr. Charles Raison.
-
Delta-9-tetrahydrocannabinol – better known as THC – is the primary psychoactive compound found in cannabis. THC binds to endocannabinoid system receptors, eliciting a wide range of physical effects and producing the “high” associated with its use. A new study suggests that THC reverses brain aging in old mice.
Researchers injected old mice with a microdose of THC that was roughly three to four orders of magnitude lower than a typical dose. Then, they assessed gene expression in the animals' hippocampal tissue at five days and five weeks post-treatment.
After just five days, they found that the microdose THC treatment altered the expression of 18 genes related to neurogenesis (the production of new nerve cells). THC altered the expression of 88 genes related to nerve cell survival and development five weeks post-treatment. Interestingly, THC did not affect brain-derived neurotrophic factor, a protein noted for its effects on neurogenesis.
These findings suggest that a single microdose of THC exerts potent, enduring effects on the rodent brain and may have potential applications in humans. It also aligns with results from a compelling case study in which THC microdosing ameliorated symptoms of Alzheimer’s disease. Lactate, a molecule produced during vigorous exercise, also has robust effects on the brain, influencing neurogenesis and promoting cognitive function. Learn more in this episode featuring Dr. George Brooks.
-
Pregnenolone could be a potential therapy to treat the detrimental effects of prenatal exposure to marijuana. (2019) www.sciencedaily.com
From the article:
A University of Maryland School of Medicine study using a preclinical animal model suggests that prenatal exposure to THC, the psychoactive component of cannabis, makes the brain’s dopamine neurons (an integral component of the reward system) hyperactive and increases sensitivity to the behavioral effects of THC during pre-adolescence. This may contribute to the increased risk of psychiatric disorders like schizophrenia and other forms of psychosis later in adolescence that previous research has linked to prenatal cannabis use, according to the study published today in journal Nature Neuroscience.
The team of researchers, from UMSOM, the University of Cagliari (Italy) and the Hungarian Academy of Sciences (Hungary), found that exposure to THC in the womb increased susceptibility to THC in offspring on several behavioral tasks that mirrors the effects observed in many psychiatric diseases. These behavioral effects were caused, at least in part, by hyperactivity of dopamine neurons in a brain region called the ventral tegmental area (VTA), which regulates motivated behaviors.
More importantly, the researchers were able to correct these behavioral problems and brain abnormalities by treating experimental animals with pregnenolone, an FDA-approved drug currently under investigation in clinical trials for cannabis use disorder, schizophrenia, autism, and bipolar disorder.
-
Intense cycling exercise at 80% maximum heart rate improves memory via endocannabinoid action on the hippocampus www.sciencedaily.com
Exercise activates the endocannabinoid system to promote learning and memory formation.
Scientists have identified robust links between physical exercise and brain health. Some of the mechanisms that drive the beneficial effects of exercise on the brain include increases in brain volume and connectivity, improved blood flow, enhanced synaptic plasticity, and increased neurogenesis – the formation of new neurons. Findings from a 2020 study suggest that moderate- to vigorous-intensity exercise improves motor sequence memory via endocannabinoid action on the hippocampus.
Motor sequence memory involves learning predefined sequences of interrelated motor actions, such as playing the piano or dancing. The hippocampus interacts with various neural networks to support the formation of motor sequency memory.
Endocannabinoids are small lipid molecules produced in the body that bind to cannabinoid receptors in the central and peripheral nervous systems. Endocannabinoids regulate many physiological processes, including movement control, pain processing, brain development, and learning and memory. The two major endocannabinoids in the body are anandamide and 2-arachindonyl glycerol.
The study involved 15 healthy adults (average age, 23 years) who had at least fair respiratory fitness, as measured via VO2 max. Participants completed a serial reaction time task (a widely used measure of learning and memory) before and after three conditions: moderate-intensity exercise, vigorous-intensity exercise, and rest. Prior to performing the task, participants consumed a standardized carbohydrate-rich breakfast. During the task, the investigators measured the participants' behavior, brain activity, and circulating anandamide (endocannabinoid) levels.
They found that vigorous-intensity exercise markedly improved motor sequence memory compared to rest. Moderate-intensity exercise also improved motor sequence memory, but to a lesser degree. The improvements coincided with increased levels of the endocannabinoid anandamide and enhanced hippocampal activity.
These findings suggest that vigorous-intensity exercise promotes motor sequence memory and learning and underscore the benefits of exercise on cognitive function. Learn about the beneficial effects of aerobic exercise in our overview article.
-
The body’s endocannabinoid system regulates communication between the immune system and gut microbiota. www.sciencedaily.com
The euphoria known as a “runner’s high” is caused by activation of the endocannabinoid system, a complex signaling system that regulates energy metabolism, inflammation, pain, and brain biology. The gut microbiota, which coordinates its activity with the brain and immune system, also modulates energy metabolism and inflammation and brain functions such as mood and cognition. Findings of a new report suggest that the endocannabinoid system is involved in communication between the gut and the immune system.
The gut microbiota, the community of microorganisms that live in the digestive tract, consume nutrients from the diet that are not absorbed by the host and produce multi-purpose compounds such as short chain fatty acids (SCFA). Previous research has demonstrated that some strains of bacteria that produce SCFAs modulate the number of cannabinoid and opioid receptors in the gut. A dysregulated endocannabinoid system and gut microbiota may increase the risk of inflammatory bowel disease, irritable bowel syndrome, and obesity; however, [exercise may improve microbiota and gut health.](https://www.hindawi.com/journals/omcl/2017/3831972/)
The authors collected baseline data from a group of 78 participants (age, greater than 45 years) with osteoarthritis who were part of a separate trial. They also collected data from a group of 40 additional adults. Participants provided a stool sample for the measurement of cannabinoids and cannabinoid metabolites, inflammatory markers, and SCFAs. They also sequenced the bacterial DNA contained in the stool sample to identify the types of bacteria present.
The researchers found that endocannabinoid concentrations in the stool increased as levels of SCFAs, SCFA-producing bacteria, and overall microbiota diversity increased. Higher endocannabinoid levels were associated with higher levels of inflammation-resolving cytokines such as interleukin-10 and lower levels of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha. Using a statistical model, the researchers found that endocannabinoid levels mediated the relationship between SCFA and inflammatory markers. This means that the relationship among these three variables is stronger than the relationship between SCFA and inflammatory markers alone.
These results demonstrate that endocannabinoids facilitate some of the anti-inflammatory effects of SCFAs and that the endocannabinoid system modulates the immune system through activity of the gut microbiota.
-
A component of cannabis may reduce colon cancer risk. www.forbes.com
The chronic inflammation that accompanies ulcerative colitis, a type of inflammatory bowel disease, increases the risk of developing colon cancer. New research in mice suggests a component of cannabis may prevent the development of colitis-associated colon cancer.
Cannabis, also known as marijuana, contains a family of chemicals called cannabinoids, including the psychoactive compound, tetrahydrocannabinol (THC). THC binds to cannabinoid receptors (CB), present throughout the body, altering appetite, pain, mood, and memory. CB1 receptors are more common in the brain, while CB2 receptors are mainly expressed by the immune system.
The investigators conducted a two-part study to determine the effects of THC on gut inflammation. In the first part of the experiment, they gave mice that had colitis THC by mouth (10 milligrams per kilogram body weight) or a placebo treatment twice weekly for nine weeks. They then measured inflammation and cancer development in the colonic tissue of the mice. The mice in the treatment group exhibited statistically significant decreases in tumor initiation and colitis severity. The authors of the study attributed this to decreased expression of the pro-inflammatory cytokine interleukin-22.
In the second part of the experiment, the investigators used a rodent colitis model to study the role of THC in regulating immune cells that express the CB2 receptor. Mice received the same dose of THC daily given to the mice in the first study for seven days or a placebo. Mice in the treatment group had markedly less colonic inflammation. The authors attributed this to decreased activation of the pro-inflammatory dendritic cells and macrophages and increased production of anti-inflammatory T-regulatory cells.
These findings may be important in the fight against colorectal cancer, but the results have their limitations. The dose of THC used in this study is equivalent to 680 milligrams for a 150-pound person, which is far greater than the 10 to 25-milligram range used in some clinical studies. A Cochrane review on the topic of cannabis use for ulcerative colitis concludes that there is insufficient evidence to make strong recommendations about THC safety and efficacy and that additional investigations of cannabis dosing are warranted.
-
THC given to old mice improved performance on memory tests. www.scientificamerican.com
THC (found in cannabis) that was given to old mice improved performance on learning and memory tests, improved connections between neurons, and resulted in gene activation profiles in the hippocampus that resembled young mice.
The mice that were 12 months old (mature mice) and 18 months old (old mice) both performed better after given THC and this on was dependant on activation of glutamatergic CB1 receptors and histone acetylation that was induced by THC.
In contrast, young mice given THC performed worse on memory tests. The mice termed “young” in this study were 2 months old. They performed worse on memory tests after given THC. Typically a mouse is termed “adult” if it is 3 months old. It seems possible that some brain development may still occur at 2 months of age but I’m not sure.
It is unclear whether THC will improve memory in older adults but this preclinical study provides strong evidence along with a mechanism that it might.
-
higher acid-sphingomyelinase associated with disease progression in Alzheimer's www.ncbi.nlm.nih.gov
“Pharmacological restoration of ASM to the normal range improves pathology in AD mice The ASM-mediated lysosomal/autophagic dysfunction in AD prompted us to examine possible therapeutic implications of this pathway. To decrease ASM in APP/PS1 mice, we undertook pharmacological inhibition using amitriptyline-hydrochloride (AMI) for 4 mo (Fig. 9 A). AMI is a known inhibitor of ASM that can cross the blood–brain barrier. At 9 mo of age, AMI-treated APP/PS1 mice exhibited decreased ASM activity compared with vehicle-treated mice (Fig. 9 B). Other sphingolipid metabolites were not changed (Fig. 9 C). Aβ levels were decreased in the AMI-treated APP/PS1 mice compared with the nontreated littermates.”
“ASM activity is known to be increased by environmental stress and in various diseases, and is elevated in AD patients (He and Schuchman, 2012). One downstream consequence of increased ASM is elevated ceramide, contributing to cell death, inflammation, and other common disease findings. Although elevated ASM is known to occur in AD, the cellular mechanisms that link ASM and AD have not been fully characterized. The data presented here suggest a previously unknown role of ASM in the down-regulation of lysosomal biogenesis and inhibition of lysosome-dependent autophagic proteolysis. The findings also establish proof of concept for ASM inhibitor therapy in AD.”
-
The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system journals.cambridge.org
Cannabidiol (CBD), the main non-psychotomimetic component of the plant Cannabis sativa, exerts therapeutically promising effects on human mental health such as inhibition of psychosis, anxiety and depression. However, the mechanistic bases of CBD action are unclear. Here we investigate the potential involvement of hippocampal neurogenesis in the anxiolytic effect of CBD in mice subjected to 14 d chronic unpredictable stress (CUS). Repeated administration of CBD (30 mg/kg i.p., 2 h after each daily stressor) increased hippocampal progenitor proliferation and neurogenesis in wild-type mice. Ganciclovir administration to GFAP-thymidine kinase (GFAP-TK) transgenic mice, which express thymidine kinase in adult neural progenitor cells, abrogated CBD-induced hippocampal neurogenesis. CBD administration prevented the anxiogenic effect of CUS in wild type but not in GFAP-TK mice as evidenced in the novelty suppressed feeding test and the elevated plus maze. This anxiolytic effect of CBD involved the participation of the CB1 cannabinoid receptor, as CBD administration increased hippocampal anandamide levels and administration of the CB1–selective antagonist AM251 prevented CBD actions. Studies conducted with hippocampal progenitor cells in culture showed that CBD promotes progenitor proliferation and cell cycle progression and mimics the proliferative effect of CB1 and CB2 cannabinoid receptor activation. Moreover, antagonists of these two receptors or endocannabinoid depletion by fatty acid amide hydrolase overexpression prevented CBD-induced cell proliferation. These findings support that the anxiolytic effect of chronic CBD administration in stressed mice depends on its proneurogenic action in the adult hippocampus by facilitating endocannabinoid-mediated signalling.