Cannabis-DMT Relationship

Tetrahydrocannabinol (THC) is considered to be the primary psychoactive constituent of cannabis. While THC provides a distinct set of subjective as well as physiological effects throughout the body, they are described as being distinctly different than a high-dose DMT experience from exogenous means. Those that have indulged in ingesting DMT or Ayahuasca might claim that there is no comparison between the effects of cannabis and the vaunted “Spirit Molecule”.

Cannabis use has gradually increased in America due to it’s legalization in a few states as well as the implementation of “medical marijuana” laws. With increasingly efficient and optimized cultivation techniques in place, the potency of the plant and secondary products have expanded exponentially. It would seem logical that people begin to report a vast array of different subjective experiences from the plant. Some people have even gone as far to claim that they have experienced full blown “DMT trips” from cannabis usage.

The question is how?
​The majority of the public that indulges in cannabis do not have the vivid, “out of world” hallucinations that accompany DMT trips. However, there could be some overlap if we are referring to low dose DMT experiences compared to high dose cannabis consumption.As we’ve covered rather extensively thus far on DMT Quest, we believe that there is likely a definitive relationship between melatonin and DMT. It appears that increased melatonin synthesis potentially lies as a signal/precursor to endogenous DMT formation. This is simply based on the hypothesis that “dreams” occur during sleep cycles which coincide with significantly elevated melatonin levels compared to waking consciousness. Whether DMT and/or Pinoline formation coincides with these dream states has yet to be verified in a clinical setting.Like we’ve cited before, a 1986 study in the journal Hormone and Metabolic Researchpublished a study observing the effects of THC on melatonin secretion. The study found that 120 minutes after ingesting THC in the form of a 1 gram Marijuana cigarette, melatonin levels were measured at an average of 4,333% higher than the original baseline and 3,000% higher than placebo. This would infer that pineal function is enhanced/altered via cannabis usage.



The difference between DMT and Ayahuasca is predominantly based on the intensity of the experience as well as the duration. DMT is generally ingested via inhalation (smoke/vapor) as oral ingestion would produce no effect due to monoamine oxidase (MAO) enzymes in the stomach/liver that would break down the compound.

Ayahuasca contains monoamine oxidase inhibitors (MAOI) that allow DMT to be orally active and provide subsequent psychedelic effect. The effects of Ayahuasca generally last for a few hours while smoked/vaporized DMT lasts for 15 minutes.

In 2010, the journal Naunyn-Schmiedeberg’s Archives of Pharmacology would publish a study observing monoamine oxidase inhibition (MAOI) from THC, anandamide, and the synthetic cannabinoid receptor agonist WIN in pig brains. The study found that THC was a significantly more potent MAO-A & MAO-B inhibitor than the other two compounds. However, in the big picture of potential MAOIs, THC is not considered to be an exceptionally powerful MAOI.

A 1997 study published in the journal Neuropsychopharmacology observed that THC administration increased the levels of dopamine and norepinephrine in the prefrontal cortex of rat brains. This is intriguing as melatonin has been observed to inhibit dopamine release throughout the mammalian nervous system and brain. It would appear that there is the potential for elevated levels of melatonin and dopamine simultaneously due to cannabis ingestion much like has been observed during REM sleep (dream) periods.

Another interesting observation from the 1997 study pertains to the increase in norepinephrine levels from THC. A 1985 study in Brain Research and a 1987 study in Physiology & Behavior observed the reversal of the analgesic (pain numbing) effects of 5-methoxy-N,N-dimethyltryptamine (5-MEO-DMT) due to norepinephrine depletion.

Some folks will claim that due to the fact that cannabis directly stimulates cannabinoid receptors (CB1 and CB2rather than serotonergic receptors (5-HT), that it’s impossible for endogenous DMT to be affected by cannabis ingestion. A 2011 review in the journal Neuropharmacology discusses the data indicating that CB1 receptors modulate the excitability of dorsal raphe serotonin neurons in the brain. 2012 study in the Journal Psychopharmacology observed that cannabinoid receptor agonists upregulated 5-HT2A receptors in the prefrontal cortex of rats. A 2013 study published in Neuroscience Letters observed that cannabinoid receptor agonists upregulated 5-HT2A receptors in the hypothalamic paraventricular nucleus of rats. A 2018 study in the journal Molecular Neurobiology found that cannabis users exuded enhanced expression of 5-HT2A-CB1 heteromers in olfactory neuroepithelium cells. Heteromers are a relatively new discovery in which receptors of the same and even different gene families can combine among themselves to generate dimers (chemical compounds composed of two identical or similar subunits) and possibly higher-order entities with unique biochemical and functional characteristics. 2018 study in the journal Neuropsychopharmacology found that chronic cannabis use promotes pro-hallucinogenic signaling of 5-HT2A receptors via the Akt/mTOR pathway. Interestingly enough (going back to the upsurge of melatonin from cannabis ingestion), it appears as though melatonin has the ability to modulate mTOR and Akt pathways. To complicate things even further, a 2015 study in the Journal of Biological Chemistry found that melatonin and serotonin signaling converges at MT2/5-HT2c receptor heteromers. In essence, for those claiming that cannabis can only affect cannabinoid receptors… it seems as though their understanding of the immense complexity of physiological signaling needs to be updated… perhaps?

In the video clip down below, Dr. Steven Barker cites the unpublished dissertation by Dr. Robert Harrison of the University of Alabama at Birmingham. In this clip, Dr. Barker describes an experiment in which LSD was administered to rats which subsequently increased their endogenous levels of 5-MEO-DMT by 1000% and DMT by 400%. He states “this suggests that there is an endogenous hallucinogen neuronal system and that many hallucinogens may not actually be true hallucinogens but endogenous hallucinogen neuronal system agonists that stimulate the release of these endogenous hallucinogens which then carry out their function on perception.”


Perhaps some of the effectiveness of cannabis in regards to pain management comes from triggering the body’s ability to synthesize 5-MEO-DMT via a noradrenergic pathway?

In 1973, the New England Journal of Medicine would publish a study regarding the effects of smoked cannabis on pulmonary function. The results stated that airway resistance fell 38 percent, specific airway conductance increased 44 percent, and a flow-volume loop increased by 45 percent. The conclusion was: “Marijuana smoke, unlike cigarette smoke, causes bronchodilation rather than bronchoconstriction and, unlike opiates, does not cause central respiratory depression.”

In 1974, the American Review of Respiratory Disease would publish a study citing the effects of smoked cannabis and oral THC on airway resistance (Raw) and specific airway conductance (SGaw) in asthmatic subjects. The results of the study were as follows: “After smoked marijuana, SGaw increased immediately and remained significantly elevated (33 to 48 per cent above initial control values) for at least 2 hours, whereas SGaw did not change after placebo. After ingestion of 15 mg of THC, SGaw was elevated significantly at 1 and 2 hours, and Raw was reduced significantly at 1 to 4 hours, whereas no changes were noted after placebo. These findings indicated that in the asthmatic subjects, both smoked marijuana and oral THC caused significant bronchodilation of at least 2 hours’ duration.”

In 1978, the American Review of Respiratory Disease would publish an additional study citing the effects of cannabis on metabolism and respiratory control. The results of the study were that smoked marijuana had stimulatory effects on metabolic rate, ventilation, and the ventilatory response to CO2.

In 1992, the American Review of Respiratory Disease would publish a study regarding the effect of smoked cannabis on ventilatory drive & metabolic rate. Much like the other studies, this one also showcased a significant reduction in airway resistance (Raw) coinciding with bronchodilation and increased airflow.

(Figure 3. from the 1992 study)

As we’ve touched upon in the past at DMT Quest, long-time DMT researcher Dr. Rick Strassman stated “We have known for nearly 60 years that the lungs make DMT.”

Alongside the effects of cannabis regarding melatonin, dopamine, norepinephrine levels, and monoamine oxidase inhibitory (MAOI) properties… it would seem pertinent to note the effects of cannabis on lung function. Perhaps the surge in melatonin synthesis from cannabis ingestion correlates with it’s bronchodilative effects? Whether this enhances the potentiality for endogenous DMT synthesis has yet to be verified but theoretically and anecdotally it seems have “legs”. If respiratory ease and potential increases from cannabis, it would seem logical that there would lie the possibility of synthesizing greater amounts of DMT from these factors.
Indolethylamine-n-methyltransferase (INMT) is an enzyme found in the body that converts tryptamine to DMT. A 2013 paper in the Public Library of Science outlined several studies that point to the fact that mice with compromised lung function exuded lower INMT expression. Perhaps it’s possible that bronchodilation and greater respiratory ability via cannabis usage could increase INMT expression and subsequently DMT synthesis?Yes… I know. Wild speculations!(It appears as though there could be a correlation between a slowed dominant EEG state (ex. Theta/Delta) and bronchodilative effects. A 2006 summary in the journal Thorax outlined the lung degrading effects of negative emotions such as anger and hostility which would coincide with a faster dominant EEG wave (ex. Beta).)

In 2014, a former “Master Shaman” named Hamilton Souther would create a field known as “Blue Morpho Cannabis Shamanism. According to Souther, when he returned to the United States from Peru, he lacked access to plants and dietary components to alleviate nerve pain from a motorcycle accident earlier in life. He then proceeded to obtain his medical marijuana card and turned to cannabis as a potential pain remedy.

As he returned to his Los Angeles apartment, he would ingest the cannabis and subsequently engage in an “ayahuasca-like experience” for 3 hours. He would try it again at a later time and induce a similar experience. According to Souther, he would begin experimenting with close friends and found that he could assist in inducing these experiences in others as well.

In perusing the forums of many different mind-body practices including meditation, Wim Hof Method, hypnosis, binaural beats, and sensory deprivation tanks, it seems as though there is a definitive potentiality to incorporate cannabis within these systems to experience endogenous DMT release. It doesn’t necessarily mean that endogenous DMT is not experienced solely through these methods but rather that there appears to lie potential based on anecdotal claims.

As we’ve reiterated prior on DMT Quest… Dr. Strassman’s trial was based on four different dosages (0.05mg/kg, 0.1mg/kg, 0.2mg/kg, and 0.4mg/kg) of DMT. The lowest two doses were considered sub-psychedelic but the participants still exuded physiological symptoms and subjective emotional shift. The greater amounts would induce dose specific intensities of the experience with the greatest “breakthroughs” at 0.4mg/kg. Nevertheless, full-blown psychedelic experiences or not, DMT was the culprit of the varying effects.

Could it be possible that cannabis elevates endogenous DMT synthesis 75% and 5-MEO-DMT 200% rather than the 400% and 1000% increase seen from LSD? Is it possible that the ingestion of high potency cannabis could elevate endogenous DMT to levels equivalent of a 0.15-0.18mg/kg DMT dose which would be considered just below the psychedelic threshold?

Perhaps there are physiological triggers that lead to increased endogenous DMT formation such as rhythmic respiration and complete darkness after cannabis administration? Perhaps these triggers allow a person to push a sub-psychedelic equivalent of 0.15mg/kg up to 0.25mg/kg in which they have “ayahuasca-like” experiences. Based on anectodal claims of ingesting cannabis edibles (50mg & higher) combined with extended time in a sensory deprivation tank (3 hours), it sure appears that “something” is definitely happening. Frequency of usage seems to play a definitive role on the experience as well.

The obvious next step in terms of cannabis research is to design a study which measures DMT levels and metabolites prior, during, and after cannabis administration. The same exact protocol outlined in the Measuring DMT Formation in Humans could be utilized for this hypothetical study. If the study does indeed show increased endogenous production of the “Spirit Molecule” due to cannabis ingestion… that wouldn’t be extraordinarily surprising.

For a more extensive look at the potential effects of DMT synthesis within the body and how they correlate with externalized and internalized experiences read this 6-part Series on DMT & Gamma Waves as well as the “Wild Theories” series.

DMT Quest is a non-profit 501(c)3 dedicated to raising awareness and funds for endogenous DMT Research. This specific field of psychedelic research has been underfunded for many decades now. It’s time to take our understanding of human physiology, abilities, and perception to the next level. E-mail me at with any comments or questions. You can also follow us at FacebookInstagram, or Twitter.