Colorado finalizes rules for psychedelic therapy training

The side effects of psychedelic drugs vary depending on the substance, dose, set, and setting of the person taking them. One leading possibility was the brain’s serotonin system, which can play a role in stabilizing feelings of well-being and happiness—the basis for MDMA’s therapeutic use. To test this question, the Malenka lab separately blocked MDMA’s ability to release either serotonin or dopamine in mice. But inhibiting serotonin prevented this effect—strong evidence for a link between this neurotransmitter and the drug’s “prosocial” effects. At the heart of the matter is the “trip,” or the acutely brain-altering experience that characterizes these psychedelic drugs.

IX. Potential Therapeutic Value for Psychedelics

A 2020 systematic review looked at four studies of MDMA and five studies of ketamine for the treatment of trauma. The evidence supporting ketamine alone was very low, while the evidence for ketamine with psychotherapy was low. The psychedelic effects of hallucinogenic drugs may help ease the effects of trauma, but research so far has produced mixed results.

Why are psychedelic drugs illegal?

Although the term entheogen is now seeing fairly wide acceptance within the culture of those who use these substances “recreationally,” a search of the term in the National Library of Medicine finds only five hits. Although it seems unlikely that the term entheogen will be adopted within the formal scientific community, the reader should realize that in some circles entheogen is generally synonymous are psychedelics addictive with psychedelic. Nonetheless, it should be appreciated that the effects produced by psychedelics are highly dependent on the set (mental expectation) of the user and the setting (environment). A set and setting designed to facilitate a mystical experience will increase the probability of such an occurrence, whereas an unstructured or party-type setting is less likely to lead to a positive outcome.

Psychedelic Drug Effects, Side Effects & Dangers

Doctors can use many different drugs in psychedelic therapy, though most recent research has looked at psilocybin, a substance found in psychedelic mushrooms. They may “reset” the brain by altering neurotransmitter levels, induce a new perspective on life by causing a person to have a mystical experience, or teach a person a new way of thinking. Some research also suggests these psychedelics increase suggestibility, making a person more open to ideas discussed in therapy.

Psilocybin may also be helpful in the treatment of depression and anxiety when these mental health conditions are specifically linked to life threatening diseases, according to a 2020 systematic review and meta-analyses of clinical trials in Biomedicines. However, because the study relied on self-reporting, it does not conclusively prove that psychedelic experiences can affect mental health. Rather, it suggests a mechanism through which psychedelics might improve mental health, which is in feeling greater self-compassion and less obsession with negative thoughts. A 2016 study of 29 people with cancer who had anxiety or depression related to their diagnosis compared those who got a single dose of psilocybin mushrooms to those who got a placebo.

• Hallucinogen is now, however, the most common designation in the scientific literature, although it is an inaccurate descriptor of the actual effects of these drugs.
• Sharif and Senchyna (2006) used RT-PCR to demonstrate that human ocular tissues expressed mRNA for the 5-HT2A and 5-HT2B receptors, with greatest abundance in the retina, ciliary body, ciliary epithelium, choroid, conjunctiva, and iris.
• Thus, Lee et al. (2007) measured H-reflex amplitude after a standardized incomplete contusive SCI in rats and measured the H-wave/M-wave ratio.
• Their potency is so high that they are often distributed on blotter papers and marketed as being LSD.
• Kometer et al. (2012) reported that psilocybin enhanced positive mood and attenuated recognition of negative facial expression.

5-HT2A receptor immunohistochemistry was performed on spinal cord sections adjacent to those used for the 5-HT immunohistochemistry. Four weeks after a mild SCI, the H-wave/M-wave ratio was significantly increased by 93 nM, but not 31 nM of DOI. Mild SCI animals had significantly more 5-HT2A receptor immunoreactivity 4 weeks after SCI than did uninjured controls. They further speculate that 5-HT2 receptor modulation of enhanced recruitment of motoneurons in response to afferent input may contribute to locomotor recovery after an incomplete SCI. If these results can be translated to humans, it suggests that administration of a 5-HT2A agonist at the site of a contusional SCI, possibly by intrathecal administration, might promote recovery from the injury.

• Use of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD) and marijuana by so-called hippies who demonstrated against the Vietnam War during the 1960s created great consternation among authorities and legislative bodies, both at the federal and state levels.
• Three different cohorts of animals were injected chronically, once a day for 8 days, with MDL11939.
• The highest dose of R-DOI administered in that study (0.3 mg/kg) is the lowest dose that can be behaviorally detected by mice (Smith et al., 2003).
• Others, like chemical compounds LSD and MDMA, also known as “ecstasy” or “molly,” originated in laboratories.
• The reduction in the P and C scores was significant after the low, medium, or high dose, whereas the reduction in the Q score was significant only after the peak effect of the high dose of psilocybin.

The most common types of psychedelics are those in the lysergic acid diethylamide (LSD), psilocybin (magic mushrooms), and mescaline (peyote) families. LSD, also known as acid, is an odorless and colorless synthesized chemical whose effects can last up to 12 hours. Psilocybin mushrooms can be eaten or brewed into a tea, with effects lasting around 4-6 hours. Short-term potential risks include anxiety, confusion and panic attacks, while long-term risks may include flashbacks, impaired judgement, psychosis and psychological dependence.

If these drugs deliver on their promised benefit, a new era for psychiatric medicine might be at hand—and all it took was for us to finally open our minds to the possibilities. This mechanistic separation between therapeutics and abuse might not be possible in all drugs, however. While scientists are still working on these varied psychedelic compounds, the risk looms that abuse potential might come as an inseparable side effect of treatment. Currently, researchers are working to develop this approach in ketamine trials, with the potential for future applications in other compounds. From what researchers have seen so far, however, there has not been compelling evidence that these drugs can work without the holistic process of preparation, “trip,” and integration. In a 2020 study, the Deisseroth lab linked these dissociative states to a specific rhythm of activity in particular circuits in the mouse brain.

Subjective reports from the two different routes of administration indicate profound differences in the speed of onset, as well as the intensity of the subjective effects. Psilocybin given orally generally takes about 40 minutes to begin to manifest its effect, with a duration of action lasting 4–6 hours. By contrast, subjective effects of 2 mg psilocybin given as an intravenous injection over 60 seconds begin at the injection period, reach a sustained peak after 4 minutes, and subside completely after 45–60 minutes (Carhart-Harris et al., 2011). Vascular responses resulting from the agonist activity of psilocin at 5-HT1 family receptors are likely to be more pronounced after intravenous drug administration. Oral administration of psilocybin followed by repeated fMRI scans would lead to perspective on the temporally related changes in blood flow/brain activation and the effects of different doses could be examined. In any event, differences in neuronal activity indices (metabolic rate of glucose, CBF, or BOLD), and differences in the intensity, dynamics, and content of psilocybin-induced symptoms could potentially account for these apparent discrepancies.

It should be pointed out that the efficacy of a psychedelic in treating a particular condition could be attributed either to a psychologic effect or to actual physiologic adaptive changes in brain neurochemistry. Therefore, in some cases, the discussion will focus on possible receptor and neurochemical mechanisms that could serve as the explanation for efficacy. In other examples, there may be no evident explanation in known physiology, and efficacy may involve novel acute psychologic mechanisms, although ultimately one is still talking about neurochemistry.