OCTOBER 28, 2022

Cannabis & Psychedelics: How They Interact

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Progress in terms of cannabis and psychedelic legalization have had severe ramifications for many people, particularly those suffering from mental illnesses or addictions. However, it raises an important question: how does cannabis interact with other psychedelics such as LSD and psilocybin? 

Unfortunately, the answer is not simple. In reality, there is little information out there in terms of publications presenting conclusive research on cannabis and psychedelic drug interactions. However, owing to a shift in views regarding drugs, getting high is no longer strictly considered a sign of deviance or cultural resistance, it’s science.

This marks a shift insofar as researchers have now been given permission to explore the effects of mind-altering chemicals, which will lead to fresh data on the effects of combining cannabis with psychedelic drugs like LSD, magic mushrooms, or ayahuasca.

With cannabis and psychedelics becoming more widely available, it’s more vital than ever to understand their effects, both alone and in combination.

Join us as we deep dive into the complexities of combining cannabis and psychedelics and summarize all pertinent material here.

How do psychedelics and hallucinogens work? 

The word “psychedelic” is Greek in origin, stemming from the words ‘ψυχή (psyche, or mind), and ‘δηλείν’ (delein, to reveal). Sometimes “hallucinogen” is used instead of psychedelics. These words are currently used to describe a class of medications noted for their mind-altering properties.

The term “psychedelic” refers to a group of medications that include a variety of substances. And, while all of these medications can cause substantial alterations in consciousness, each has its own distinct mode of action.

Traditional psychedelics and hallucinogens operate on the 5-HT2A serotonergic receptor. Lysergic acid diethylamide (LSD), psilocybin, mescaline, and N,N-dimethyltryptamine are among them (DMT). These medications’ effects are frequently described as psychotomimetic, or simulating psychotic or schizophrenia-like states.

Entheogens (also known as Entactogens) are another form of psychedelic substance. The phrase comes from the Greek words “entheos”; to be inspired or filled with God and “genesthai”, to come into being. In ceremonial or religious situations, these chemicals are known to elicit intense sensations of love, connection, and empathy. Ayahuasca, peyote cactus, hallucinogenic mushrooms, and Salvia Divinorum are all examples. This group also includes MDMA (3,4-methylenedioxymethamphetamine).

NMDA antagonists, also known as dissociative agents, are another type of drug that is sometimes classified as a psychedelic. One type of drug in this category is ketamine. 

Cannabis is a psychedelic drug, right?

For thousands of years, cannabis has been widely utilized in spiritual contexts.

Spiritual cannabis usage in India may date back to primordial times. Cannabis usage in Judahite worship has been traced back to the seventh century BCE, according to research. In Jamaica, smoking ganja in a chillum pipe is frequently considered a sacred rite.

A study published in the Journal of Cannabis Research questioned 319 people about their cannabis and psychedelic drug usage. They discovered two forms of cannabis use: recreational and spiritual. One-quarter of individuals polled thought cannabis was an entheogen, with researchers noting:

“These spiritual cannabis users…reported cannabis experiences that resembled psychedelic experiences in certain ways…”

Entheogenic experiences were described by interviewees as “marked by insight into oneself, relationships, and the world, inner visions, emotions of serenity, joy, and love, and occasional peak experiences involving ego disintegration and communion with transcendent energies.”

Chronic cannabis usage, like classical hallucinogens, can change 5-HT2A receptor function. Cannabis can also induce psychotomimetic states similar to those produced by ketamine, adding to the notion that cannabis can have psychedelic-like effects.

It is vital to highlight that chronic cannabis use, particularly Type I cannabis, as well as psychedelic usage, may raise the risk of schizophrenia and psychosis. However, much of the evidence implies that this linkage is linked to a genetic susceptibility to schizophrenia.

Understanding Drug Interactions is Critical

When two drugs are taken at the same time, drug interactions can develop. The nature of these interactions is determined by a variety of factors, including the patient’s health and the type of medications eaten.

Drug interactions have three major effects:

  1. Additive (1 + 1 = 2)

  2. Synergistic (1 + 1 > 2)

  3. Antagonistic (1 + 1 < 2)

According to a 2012 meta-analysis, significant medication interactions were the cause of hospitalization in 7% of instances. Understanding possible medication interactions is therefore critical to reducing the risks associated with pharmacological therapy and is an useful method to prevent or anticipate any adverse effects that may arise.

Why Set & Setting are Essential

To comprehend how cannabis reacts with other psychedelics, we must first discuss context and setting.

In the 1950s and 1960s, American scientists set out to discover how LSD impacted users. Despite their best efforts, scientists were unable to determine “standard effects,” i.e. how a medicine should or normally acts.

According to researchers, psychedelics’ subjective effects were not entirely determined by their pharmacology.

Set and setting, or mindset and setting, were proposed as a reason why some people responded well to psychedelics while others did not. The set and location are supposed to have an impact on whether you have a “good” or “poor” experience. The sort of psychedelic experience you will have is a major factor in determining how cannabis will interact with any specific psychedelic.

Interactions between Cannabis & LSD

The notion that cannabis is a lesser variant of LSD is not novel. In fact, Dr. Harris Isbell, a former CIA official, published a paper in 1969 concluding that large dosages of THC might produce hallucinations akin to LSD.

Recent breakthroughs in marijuana research have supported Dr. Isbell’s findings. A 2013 study discovered that cannabinoid receptor agonists, or chemicals that activate receptors to cause a response, increased the expression of 5-HT2A serotonergic receptors in rats. The process through which cells boost their biological reactions to stimuli is known as upregulation.

The 5-HT2A serotonin receptor is implicated in the majority of classic psychedelics and is responsible for a range of activities. Dysregulation at this receptor site has also been associated to a number of illnesses, including mental disorders (anxiety, depression, and schizophrenia) as well as headaches and hallucinations.

Another 2018 study discovered that prolonged THC exposure “produced a pro-hallucinogenic molecular conformation” of the 5-HT2AR receptor in mice, which “exacerbated schizophrenia-like reactions.”

LSD is a potent 5-HT2A agonist, with a higher binding affinity for the receptor than serotonin itself. LSD is also highly attracted to additional 5-HT receptors, making it difficult to anticipate its pharmacologic effects.

These data imply that combining cannabis and LSD may have an additive or synergistic impact, particularly on visual hallucinations. This impact, however, is inherently subjective. Factors such as dosage, set, and environment impact whether or not you have a pleasant or poor experience.

According to prevailing opinion, if you’re having a “good trip,” cannabis may improve the experience, and if you’re having a “poor trip,” cannabis may detract from it. Another key component that is mostly underexplored is the cannabis chemovar ingested.

Cannabidiol (CBD) is being studied for its antipsychotic properties. Taking CBD alongside other psychedelics may diminish their psychomimetic effects, although this link is unknown.

LSD, like cannabis, is relatively safe at psychoactive dosages and has a limited abuse potential when compared to many other drugs. There have been no reported LSD overdose deaths.

How Cannabis & Psilocybin Interact

Psilocybin is the principal component present in “magic mushrooms,” and it is transformed to its more active form, psilocin, when consumed.

Psilocybin and psilocin, like LSD, are classic hallucinogens that function as 5-HT2A agonists. Remarkably, anecdotal accounts of different strains of mushrooms having varying effects, similar to cannabis, exist.

When used with psilocybin, cannabis can have a drastically different effect. In 2019, the pro-psychedelic newspaper Double Blind polled 90 persons who have used cannabis and psychedelics together. The newspaper also spoke with medical specialists about the consequences of mixing cannabis and psychedelics.

According to Dr. Nikola Djordjevic, Medical Advisor at Loud Cloud Health, “…many people’s perceptions are improved when they mix cannabis with psilocybin.”

Reflective thinking is a subjectively stated experience that distinguishes LSD from psilocybin. On mushrooms, psychedelic users commonly describe having deeper emotions of introspection or inward-facing excursions. This may help explain why combining cannabis and psilocybin may cause more unpleasant responses (especially mental agitation and anxiety) than LSD.

Interactions Between Cannabis & DMT/Ayahuasca

In the body, N, N-Dimethyltryptamine, or DMT, is an endogenous hallucinogen. Dreams are thought to be caused by this hormone, which is produced in the pineal gland.

South American plants produce ayahuasca, a hallucinogenic, entheogenic drink. Both DMT and MAO-inhibiting harmala alkaloids are found in plants commonly used to make ayahuasca, preventing the body from breaking down the DMT. 

DMT, or N, N-Dimethyltryptamine, is an endogenous hallucinogen, which means it is created by the body. It is generated in the pineal gland and is considered to be responsible for dreaming.

Ayahuasca is a hallucinogenic, entheogenic beverage made from different South American botanicals. Ayahuasca plants contain both DMT and MAO-inhibiting harmala alkaloids, which hinder the body from breaking down the DMT and so prolong the psychedelic experience.

While DMT has been demonstrated to interact with a variety of receptors when delivered exogenously, it primarily operates on the 5-HT2A receptor. As a result, mixing THC and DMT may have an additive or synergistic effect, whilst CBD may have an antipsychotic impact.

Interactions Between Cannabis & Mescaline (San Pedro/Peyote)

Mescaline is a classic hallucinogen that is present in the San Pedro and Peyote cacti. It is also a partial agonist with significant affinity at the 5-HT2A receptor location.

Mescaline has effects that are similar to LSD but require a greater dose to induce such effects. Doses of 300-500 mg can cause “…olfactory or auditory hallucinations, illusions, depersonalization, and anxiety depressive symptoms,” as well as perspiration, nausea, vomiting, and tremor. Despite these undesirable side effects, mescaline-containing cacti are often seen to be gentler and more introspective than other psychedelics, which may be owing in part to partial agonism at 5-HT2A. This is the same idea behind the effects of whole-plant cannabis vs synthetic cannabinoids.

There hasn’t been much study done on the pharmacological reactions between cannabis and mescaline. Combining cannabis with mescaline may potentially have an additive or synergistic effect. This, like LSD, is a subjective experience. This implies that depending on the set/setting and an individual’s unique sensitivities to cannabis, the synergistic impact will make a trip more enjoyable or more awful. Because of its anti-emetic qualities via 5-HT, cannabis, particularly CBD, may also help relieve some of the nausea and tremors associated with mescaline usage.

Interactions Between Cannabis & Ketamine

Ketamine is a one-of-a-kind drug. It’s formally classed as an anesthetic, or a pain-relieving chemical. It is often used to generate severe sedation in hospital emergency departments and operating rooms.

Ketamine, unlike conventional hallucinogens, works largely on the NDMA receptor rather than the 5-HT2A receptor. It is classified as a psychedelic because of its capacity to operate as a dissociative agent while also producing psychomimetic and psychedelic effects in a dose-dependent way.

Unlike the other chemicals on this list, researchers have shown that “…the safety profile of ketamine appears to be changed when taken in a polydrug way.”

A 2012 study published in the Journal of Clinical Anaesthesia discovered that mixing ketamine with cannabis resulted in even more pain relief. This prompted researchers to speculate that ketamine and cannabis could work in tandem at one or more receptors.

In terms of pharmacology, cannabis and psychedelics have a lot in common. Anxiety, depression, and post-traumatic stress disorder are among the conditions that currently lack effective treatments. In the new era of drug policy, these two classes of drugs – cannabinoids and psychedelics – will be frequently discussed.

In conclusion, the researchers state that their findings might have significant implications for the therapeutic use of psychedelics since “several of the therapeutically desired psychological effects associated with psychedelics may, in principle, be increased by contemporaneous cannabis use.”

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