Understanding Psychadelics
- vzuluagacuartas
- Sep 29, 2019
- 11 min read
Updated: Dec 7, 2019
Over the past 10-15 years, the use of psychedelic drugs for the treatment of mental health issues has been widely studied. However, there is minimal trust regarding the legitimacy of such therapeutic properties (Walsh, 2016). If psychedelic drugs are legalized to aid in the betterment of mental health problems, then would individuals with no mental health illnesses benefit from the legalization of such drugs?
By definition, psychedelics are a "type of drug capable of reliably bringing about states of altered perception, thought, and feeling that are not usually experienced, besides in dreams or during religious exaltation" (Jaffe, 1990). According to Elsey (2017) the most common psychedelics are: dimethyltryptamine (DMT—found in ayahuasca), lysergic acid diethylamide (LSD), mescaline (found in peyote), and psilocybin (found in ‘‘magic mushrooms’’).
The problems of legalization come from the misunderstood effects of hallucinogenic drugs, such as LSD. During the 1970's, science focused its attention on false claims. These claims stated that hallucinogens caused chromosomal damage and birth defects in children born to mothers who had taken LSD during pregnancy. In later years, scientists demonstrated that such claims were false, but because of the controversial nature of the U.S. drug policy and its influence in government-sponsored research of illicit drugs, the media ignored the fact that such claims were false (Jennings 2003; Muneer 1978). Unfortunately, the therapeutic benefits of hallucinogenic use have been judged by its abuse, affecting the availability of the drugs for clinical use. In other words, medical practitioners' opinions and drug legislations have made the scientific study of hallucinogens limited, as they have cut off funding from research laboratories.
According to the National Institute of Drug Abuse, 33% of the population in The United States of America aged 12 and older have experimented with hallucinogenic drugs at least once in their lifetime as of 2018. Hence, 33% of the population was once involved in illegal activities. That is an incredibly large number!
How do psychedelics work?
There are two principal stages after psychedelic consumption. The first stage is known as the "acute psychedelic state," where consciousness is significantly altered and individuals go through mystical experiences (e.g.merging with the universe, sense of unity, transcendence of time and space, and connectedness, etc...)
Many individuals participating in hallucinogenic therapies have insinuated that such experiences have been therapeutic and emotionally energizing!
The second stage is known as the "psychedelic afterglow," in which individuals have an increased positive mood and rumination halts. The second stage is known to last for years, depending on the significance of the discoveries found during the trip.
Quick review of the neurobiology of psychedelics:
Past research has linked the use of psychedelic drugs to structural and neuronal changes in brain regions
that are involved in rumination, self-reflection, critical thinking, and other metacognitive processes (metacognition means awareness and understanding of one's own thought processes). two of the regions are the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC). Both regions constitute the default mode network (DMN). The default mode network is a group of brain regions that seem to show lower levels of activity when we are doing a specific task, but higher levels of activity when we are awake and not involved in any specific mental exercise. (Raichle and Snyder, 2007; Carhart-Harris et al., 2014; Raichle et al., 2001).
While the method of action of serotonergic psychedelics is not fully understood yet, there are many theories that support the psychedelic's affinities for various 5-HT receptors; in particular 5-HT1A, 5-HT2A, and 5-HT2C (Halberstadt & Geyer, 2011; Nichols & Sadders-Busch, 2001; Rup, 2017) .
What we do know is that:
The regions of the brain affected by hallucinogens are rich in 2A (5-HT2A) receptors.
The 5-HTA receptors are known for their involvement in serotonin ("the happy chemical") production, but hallucinogens don’t flood the brain with serotonin.
Psychedelics have very strong structural similarities to serotonin itself, which partially explains the affinity for certain 5-HT sites.
Psychedelic drugs act primarily as agonists in the 5-HT2A receptors. These receptors are expected to be the ones acting when individuals experience an alteration of consciousness (Kraehenmann et al., 2017; Preller et al., 2017).
Past hypotheses explained the effect of psychedelics through the antagonism of 5-HT1A receptors. It was believed that psychedelics completely inhibited the firing of serotonergic neurons in the dorsal (DRN) and median (MRN) raphe nuclei (Halberstadt & Geyer, 2011; Nichols & Sadders-Busch, 2001; Rup, 2017).
The evidence outlined above led to the "pre-synaptic hypothesis," which states that by selectively depressing the activity of neurons in the DRN, hallucinogens removed the inhibition of downstream neurons mediated by 5-HT receptors. It was theorized that LSD and related agents induced hallucinogenic effects indirectly by disinhibiting brain regions targeted by DRN efferents (Halberstadt & Geyer, 2011; Nichols & Sadders-Busch, 2001; Rup, 2017).
Present research has demonstrated that the psychoactive effects are more likely due to the activation of serotonin 2A receptors. Research demonstrated that 2A receptors were central to the action of hallucinogens, because blocking them with an antagonist called ketanserin decreased the occurrence of the hallucinatory state (Halberstadt & Geyer, 2011; Nichols & Sadders-Busch, 2001; Rup, 2017).
We know that psychedelics have been noticed for its therapeutic benefits in patients with mental health illnesses, but how do they help healthy individuals?
"Healthy" individuals, this is what research demonstrates:
Here is what the classic studies stated:
A classic study performed by Pahnke (1963) studied the mystical properties of psilocybin administration in healthy participants. Twenty students from a theological seminar were given either psilocybin doses or nicotinic acid (an active placebo). The students then attended a Good Friday Mass and then were assessed on the degree of spirituality felt during the mass. The majority of students found the mass to be enlightening, but twenty-seven years later, those students who were administered the psilocybin doses still felt the benefits from the mass and demonstrated an increased appreciation for life, nature, relationships, and emotions.
Another classic study performed by Savage et al., (1966) tested the effects of LSD assisted psychotherapy in healthy individuals that expressed minimal meaning in their lives. These individuals then showed higher self reported scores of self-actualization and creativity. Participant's sense of meaning was re-evaluated and they expressed feelings of unity, a greater sense of purpose, and decreased worry for the need of superficial pursuits.
Here is an example of new studies that still support the findings from classical studies:
Griffiths et al. (2008) administered healthy volunteers psilocybin. After fourteen months of follow ups, almost 60% of the participants expressed the psilocybin experience as being the most meaningful and satisfactory experience in their lives, increasing personal well-being and satisfaction.
Check more recent studies from Schmid et al. 2015, and Liechti et al., 2017. *References are below.*
Researchers have concluded that psychedelic use is beneficial for any individual who is searching for a sense of meaning and purpose (Elsey, 2017).
These drugs sound magical...then why are they seen as bad?
Apart from psychedelic's heavenly effects, there are always adverse effects that can be detrimental to an individual's life. Griffiths et al. (2008) do a great job summarizing possible risks.
Some risks are:
Acute panic attacks - these can develop into model psychotic episodes (such as jumping off a bridge by thinking one can finally fly).
The manifestation or exacerbation of psychiatric conditions.
Perceptual disturbances that may last for a long time.
Possible development of an abusive pattern of drug use (i.e, drug addiction).
Even though the side effects are not present in the majority of the population, there will always be some type of risk if psychedelics are not administered under controlled, safe environments.
Drug Policies involving psychedelics:
In certain areas, the use of psychedelics has been allowed in certain religious ceremonies (i.e., Religious groups such as the Santo Daime and Unia˜o de Vegetal and Native American Churches). Such exemptions for religious purposes allow for discussion on whether the term religion is being used for an illegal consumption of psychedelic drugs (Elsey, 2017).
However, there has been debate regarding the allowance of psychedelic drugs for treatment purposes. The issue lies in defining the purpose of the drug. There is not an exact definition on the distinction between treatment and enhancement, or between therapeutic and recreational use (Elsey, 2017).
In Canada, hallucinogens like psilocybin and LSD are controlled under Schedule III of the Controlled Drugs and Substances Act (CDSA). This means that activities such as the sale of, possession of, and production of these substances are prohibited, unless authorized for clinical trial or research purposes under Part J of the Food and Drug Regulations Act.
According to the Government of Canada (2019), currently there are no approved therapeutic products containing psilocybin in Canada.
Even though psychedelics are illegal in Canada, mushroom spore kits and grow kits are legal and are sold openly in stores, or on the internet. The "issue" is that Psilocybin and Psilocin are illegal to possess, obtain, or produce without a prescription or license. Therefore, there is a loophole in the law when it comes to the possession and use of these substances. But hey...you can buy a growing kit and have nice looking
mushrooms sitting on a pile of vermiculite.
So what is the problem with allowing psychedelic therapy in medical settings?
Firstly, if there is no clear definition of pathology, then there is no clear definition of who will need the therapy. It is difficult to have specific visible symptoms when talking of mental illness; therefore, practitioners have to infer based on how significant it is compared to the population (Elsey, 2017).
For example, there are many ways in which anxiety or depression can be expressed. Sometimes, the symptoms will be so general that there are many possibilities of misattribution.
Secondly, because an individual seems fine, one can not conclude that they are not in need of assistance for the improvement of well-being. Perhaps, if a clear definition of therapy was developed, then it would be easier to legalize the use of psychedelic drugs for medical purposes.
The aspects that make psychedelics attractive as a therapeutic drug is that they are cheap, they have a low probability of creating drug dependence, and they have more benefits than adverse effects. Regardless, they are illegal in many countries, including Canada and the United States of America. Therefore, the permission for psychedelic research is limited and the policy standards that need to be fulfilled are near impossible and costly to meet.
In order for psychedelic research to be available and effective, psychedelics must be reclassified and therapeutic potentials must be highlighted. It is difficult to know what the safest and the most optimal step towards changing drug policies is. Some suggestions are to enhance the understanding of the benefits that drugs can have when used appropriately in a control environment and to realize that psychedelics can produce lasting changes in well-being and purpose with only a single dose.
Article Summaries:
1.
A study performed by Kraehanmann et al., (2017) aimed to test the hypotheses that LSD produces dream-like waking imagery. This imagery depends on 5-HT2A receptor activation and is related to subjective drug effects. According to past research, LSD is a mixed serotonin and dopamine receptor agonist, which induces an altered state of consciousness that resembles dreaming.
Kraehanmann et al., (2017) performed a double-blind, within-subjects study design. They compared the post-peak effects of LSD, placebo, and LSD after pre-treatment with ketanserin on cognitive bizarreness during a guided mental imagery task in relation to the effects on subjective experience. In the study, 25 healthy subjects performed an audio-recorded guided mental imagery task seven hours after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). Moreover, the state of consciousness was also measured using a questionnaire called Altered State of Consciousness (5D-ASC).
The results of the study demonstrated that LSD, compared with placebo, significantly increased "cognitive bizarreness," which was correlated with the loss of cognitive control and self-boundaries. The administration of Keranserin blocked LSD effects. Therefore, the loss of effects due to the administration of Keranserin lead to the support that LSD created mental imagery similar to dreaming, primarily via activation of the 5-HT2A receptor. This was in relation to loss of self-boundaries and cognitive control.
Research regarding the neuronal effect of psychedelics in the brain is still very limited. There are many hypotheses that state differences of mechanisms that psychedelics have within the 5-HT receptors. Some research supports the agonism of 5-HT2A receptors, other research believes that the hallucinations are not caused by 5-HT2A receptors, but that they are the result of 5-HT2C agonism. Regardless, the majority of recent research has supported the 5-HT2A receptor agonism hypothesis, and in present times, it is the hypothesis that is used to explain the effects of drugs such as psilocybin, LSD, peyote, etc... Even though this research demonstrates the effects of LSD in 5-HT receptors, it lacked an explanation on the reasoning behind dream-like states when consuming psychedelics. It focused on the structures, but not on the explanations of the mechanisms that allow for hallucinations or the alterations of consciousness. Further research should implement the idea that psychedelics act as agonist of the 5-HT2A receptor and also explain why the activation of this receptor is of importance for the betterment of mental health.
2.
A study performed by Schmid et al., (2015) intended to investigate the subjective and autonomic effects of LSD.
In a double-blind, randomized, placebo-controlled, crossover study, an LSD dose of 200 μg and placebo dose were administered to 16 healthy subjects. Eight of them were male and the other eight were female. The researchers studied psychometric scales, investigator ratings, PPI of the acoustic startle response (a phenomenon in which a weak acoustic auditory stimulus inhibits a startle response induced by the subsequent presentation of a loud sound), as well as autonomic, endocrine, and adverse effects.
Waking consciousness was highly affected in healthy subjects who were part of the experimental group with LSD. The main effects seen were visual hallucinations, audiovisual synesthesia, and a derealization and depersonalization. Moreover, compared to the placebo group, subjects that were subjected to LSD doses had stronger subjective feelings of happiness, well-being, closeness to others, openness, and trust. PPI was also decreased in the experimental group.
Furthermore, physically speaking, LSD increased body temperature, blood pressure, heart rate, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine. These effects were not longer seen after 72 hours of LSD administration. Overall, the study revealed statistically significant findings and controlled for biased information. Regardless, more than one dose of LSD should have been administered to provide dose-response data. Also, subjective expectations may have influenced the psychological effects of LSD, because all of the subjects knew that they would receive LSD or placebo and not another active drug.
Regardless, the results of this study allow for a scientific understanding of the physiological effects in healthy individuals when using LSD. Endocrinological changes were related to homeostatic stress and subjects did not seem to experience any major side effects. In conclusion, LSD can be used safely, but it produces significant sympathetic stimulation.
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