It is no secret that the legislation of many countries is particularly strict with regard to drugs that, even theoretically, can cause physical or mental dependence. Moreover, it is particularly intolerant of specific classes of drugs — painkillers, psychostimulants and anesthetics, but turns a blind eye to the presence of harmful phenobarbital in the free sale (as part of some combined sedatives).
We will tell you about cases in which drugs that were legal became illegal and then returned to clinical practice.
For a long time, doctors could not safely prescribe fentanyl patches or opioid painkillers: the responsibility was too great and the bureaucratic procedure too cumbersome.
Interestingly, narcotic (opioid) painkillers in the form of patches are common in many countries. Even if the drug in this form falls into the hands of a person who really wants to «get high» or even has an addiction, it will not help him to take away the withdrawal and get the long-awaited opioid high. The fact is that the rate of release of the same fentanyl into the bloodstream is very slow, and simple and home-accessible methods of «isolating it from the patch» are currently unknown.
We will tell you about cases in which drugs that were legal became illegal and then returned to clinical practice.
For a long time, doctors could not safely prescribe fentanyl patches or opioid painkillers: the responsibility was too great and the bureaucratic procedure too cumbersome.
Interestingly, narcotic (opioid) painkillers in the form of patches are common in many countries. Even if the drug in this form falls into the hands of a person who really wants to «get high» or even has an addiction, it will not help him to take away the withdrawal and get the long-awaited opioid high. The fact is that the rate of release of the same fentanyl into the bloodstream is very slow, and simple and home-accessible methods of «isolating it from the patch» are currently unknown.
Phencyclidine
Many drugs that are currently banned are «model drugs» when describing certain pharmacological processes or phenomena.
For example, phencyclidine (aka sernyl, aka PCP) was used for general anesthesia for 15 years (from 1950 to 1965). Later it was removed from routine clinical use, but it remained in experimental pharmacology as a substance which in certain amounts causes acute psychosis, indistinguishable from psychosis in schizophrenia (this was written about, in particular, by R. Garey and E. Luby).
In his article, Garey used the term «schizophrenomimetic» — a substance whose effects are very similar to the symptoms of schizophrenia. This notion further mutated into «psychotomimetic» — a substance imitating psychosis (of any nature), and further on this term began to be used along with the word «psychedelic».
Many drugs that are currently banned are «model drugs» when describing certain pharmacological processes or phenomena.
For example, phencyclidine (aka sernyl, aka PCP) was used for general anesthesia for 15 years (from 1950 to 1965). Later it was removed from routine clinical use, but it remained in experimental pharmacology as a substance which in certain amounts causes acute psychosis, indistinguishable from psychosis in schizophrenia (this was written about, in particular, by R. Garey and E. Luby).
In his article, Garey used the term «schizophrenomimetic» — a substance whose effects are very similar to the symptoms of schizophrenia. This notion further mutated into «psychotomimetic» — a substance imitating psychosis (of any nature), and further on this term began to be used along with the word «psychedelic».
LSD
The 1950s and 1960s gave mankind not only phencyclidine, but also LSD. For a long time, this word did not have a negative connotation either. For example, Ronald A. Sandison researched the clinical use of LSD and wrote a very interesting book with a detailed description of the symptoms of drug-induced psychosis when using psychomimetic substances (1964).
Early in his research career, the psychedelic effects of LSD were described under controlled conditions and in the presence of physicians. In addition, psychiatrists in the clinics injected themselves with 100 mcg of the substance and recounted their experiences. After the trip, the psychiatrists «successfully went about their usual business»: just imagine, you find yourself in a mental hospital, and the doctor just came back to reality himself!
Psychiatrists found that LSD acts differently on healthy people and patients with neuroses and neurosis-like disorders: the latter had increased negative symptoms and were observed five times more often than healthy people.
The 1950s and 1960s gave mankind not only phencyclidine, but also LSD. For a long time, this word did not have a negative connotation either. For example, Ronald A. Sandison researched the clinical use of LSD and wrote a very interesting book with a detailed description of the symptoms of drug-induced psychosis when using psychomimetic substances (1964).
Early in his research career, the psychedelic effects of LSD were described under controlled conditions and in the presence of physicians. In addition, psychiatrists in the clinics injected themselves with 100 mcg of the substance and recounted their experiences. After the trip, the psychiatrists «successfully went about their usual business»: just imagine, you find yourself in a mental hospital, and the doctor just came back to reality himself!
Psychiatrists found that LSD acts differently on healthy people and patients with neuroses and neurosis-like disorders: the latter had increased negative symptoms and were observed five times more often than healthy people.
Contrary to popular misconception, LSD does not cure schizophrenia, but rather exacerbates its symptoms.
In addition, Ronald A. Sandison described protracted psychoses after a single ingestion of the substance, when patients changed behavior.
But more recent work has added a more generalized definition describing the long-term aftereffects of LSD: long-term hallucinogen-induced perceptual disorder (HPPD). This condition includes not only behavioral disorders but also a «visual snow» effect: individuals who have used LSD may experience a «grainy film effect» (or, as the subjects put it, a «TV interference effect»). This looks something like this:
In addition, Ronald A. Sandison described protracted psychoses after a single ingestion of the substance, when patients changed behavior.
But more recent work has added a more generalized definition describing the long-term aftereffects of LSD: long-term hallucinogen-induced perceptual disorder (HPPD). This condition includes not only behavioral disorders but also a «visual snow» effect: individuals who have used LSD may experience a «grainy film effect» (or, as the subjects put it, a «TV interference effect»). This looks something like this:
So what clinical use can LSD, supposedly the safest psychedelic, have? Paradoxically, in some cases this substance is able not to aggravate but, on the contrary, to treat anxiety disorders.
These days in Switzerland, the birthplace of LSD's «father», Albert Hoffman, scientists are investigating whether the substance can be used as a sedative in somatically healthy people and in people undergoing palliative care (for example, in the terminal stages of cancer).
This clinical trial is conducted according to all the canons of evidence-based medicine. It is placebo-controlled, with strict selection of volunteers and «blinding» — no one, including medical staff and patients, will know who was given the pacifier and who was given the active ingredient.
This trial will last until 2025, after which the results will be published, and if they prove positive, LSD could be introduced into psychiatric practice in many countries. They are also studying whether LSD can be used to treat cluster headaches, an extremely distressing form of migraine.
These days in Switzerland, the birthplace of LSD's «father», Albert Hoffman, scientists are investigating whether the substance can be used as a sedative in somatically healthy people and in people undergoing palliative care (for example, in the terminal stages of cancer).
This clinical trial is conducted according to all the canons of evidence-based medicine. It is placebo-controlled, with strict selection of volunteers and «blinding» — no one, including medical staff and patients, will know who was given the pacifier and who was given the active ingredient.
This trial will last until 2025, after which the results will be published, and if they prove positive, LSD could be introduced into psychiatric practice in many countries. They are also studying whether LSD can be used to treat cluster headaches, an extremely distressing form of migraine.
From a drug to increase blood clotting to a cure for PTSD
Let's go back to the beginning of the twentieth century. The clouds of the coming war were gathering over Europe, women in labor and aristocrats were often dying from hemorrhages, and there were no effective blood-relieving drugs. And then came the bleeding-stopping drug hydrastinine, of which MDMA (methylenedioxymethamphetamine) is a semiproduct.
For a long time, MDMA was considered just an unnecessary reaction product, until in 1927 chemist Max Oberlin decided to reveal the physiological effects of the substance.
Not only did he repeat the synthesis from the Merck patent, but apparently he actually tested its effects: he mentioned «effects on pupil size» even before Alexander Shulgin [an American chemist who synthesized and studied MDMA and other psychedelics].
In addition, before Shulgin, the U.S. military was also interested in MDMA. In 1953, they funded research into the effects of the substance, and the results of those tests were not declassified until the 1970s. Even professional historians cannot give an exact date when people first started using MDMA.
Let's go back to the beginning of the twentieth century. The clouds of the coming war were gathering over Europe, women in labor and aristocrats were often dying from hemorrhages, and there were no effective blood-relieving drugs. And then came the bleeding-stopping drug hydrastinine, of which MDMA (methylenedioxymethamphetamine) is a semiproduct.
For a long time, MDMA was considered just an unnecessary reaction product, until in 1927 chemist Max Oberlin decided to reveal the physiological effects of the substance.
Not only did he repeat the synthesis from the Merck patent, but apparently he actually tested its effects: he mentioned «effects on pupil size» even before Alexander Shulgin [an American chemist who synthesized and studied MDMA and other psychedelics].
In addition, before Shulgin, the U.S. military was also interested in MDMA. In 1953, they funded research into the effects of the substance, and the results of those tests were not declassified until the 1970s. Even professional historians cannot give an exact date when people first started using MDMA.
Alexander Shulgin, who is referred to as the «father of MDMA», did not begin to seriously study the effects of the substance until the 1970s.
It was then that psychotherapists also became interested in the substance, trying, however, not to sensationalize its use, although psychologist Leo Zeff gave a very positive description of its effects. However, the substance left the confines of laboratories and hospitals, becoming one of the «basic foundations» of the nascent rave culture.
Unfortunately, uncontrolled use of the substance often resulted in overdoses and the distribution of low-quality batches. The use of MDMA began among those who should not do so outside of a psychiatrist's office, for example, people with neurotic disorders.
The psychotherapeutic potential of MDMA was investigated in detail by American psychiatrists and psychotherapists Debbie Harlow, Alice Ager and Rick Doblin. The latter also co-founded MAPS, the Multidisciplinary Association for the Study of Psychedelics.
Doblin pursues pro-drug policy not from the perspective of a social activist or anyone else, but from the perspective of someone who did his doctoral dissertation at Harvard on the social consequences and legal aspects of regulating the circulation of psychoactive substances.
It was then that psychotherapists also became interested in the substance, trying, however, not to sensationalize its use, although psychologist Leo Zeff gave a very positive description of its effects. However, the substance left the confines of laboratories and hospitals, becoming one of the «basic foundations» of the nascent rave culture.
Unfortunately, uncontrolled use of the substance often resulted in overdoses and the distribution of low-quality batches. The use of MDMA began among those who should not do so outside of a psychiatrist's office, for example, people with neurotic disorders.
The psychotherapeutic potential of MDMA was investigated in detail by American psychiatrists and psychotherapists Debbie Harlow, Alice Ager and Rick Doblin. The latter also co-founded MAPS, the Multidisciplinary Association for the Study of Psychedelics.
Doblin pursues pro-drug policy not from the perspective of a social activist or anyone else, but from the perspective of someone who did his doctoral dissertation at Harvard on the social consequences and legal aspects of regulating the circulation of psychoactive substances.
After MDMA was banned in the mid-1980s, pharmacologists, strangely enough, took up the substance again - now armed with more modern toxicity assessment techniques. Since then, there has been a theory of MDMA's neurotoxicity that has both supporters and opponents - and both sides have arguments backed up by experimental research. At the same time, both consider the opponents' methodologies for assessing the substance's effects to be incorrect.
Clinical trials of MDMA-Assisted Psychotherapy (MDMA) are now underway. In this case, taking MDMA differs from using it under loud techno and EBM in that it is supervised by a psychiatrist or psychotherapist.
The specialists first assess the patient's physical and mental condition (mainly they check to see if the patient has any serious cardiovascular and mental illnesses that MDMA can exacerbate).
MAPS is also testing MDMA as an aid to patients with post-traumatic stress disorder (PTSD, an official clinical trial registry entry). Similar tests are also being conducted at the University Hospital Basel in Switzerland.
Clinical trials of MDMA-Assisted Psychotherapy (MDMA) are now underway. In this case, taking MDMA differs from using it under loud techno and EBM in that it is supervised by a psychiatrist or psychotherapist.
The specialists first assess the patient's physical and mental condition (mainly they check to see if the patient has any serious cardiovascular and mental illnesses that MDMA can exacerbate).
MAPS is also testing MDMA as an aid to patients with post-traumatic stress disorder (PTSD, an official clinical trial registry entry). Similar tests are also being conducted at the University Hospital Basel in Switzerland.
Cannabis
And how is one of the most common and controversial drugs out there, marijuana? Struggling: With the help of evidence-based medicine, marijuana is trying to carve out its own small patch of use in the therapy of various diseases.
The aforementioned Rick Doblin was one of the first to conduct a rigorous, systematic study that justified the use of marijuana and marijuana-based medicinal forms: they help prevent vomiting and nausea in cancer patients.
The article, published back in 1991 in the authoritative medical journal Journal of Clinical Oncology, ended with the following conclusions: about half of oncologists in one form or another recommended their patients to use marijuana to relieve their symptoms. The same percentage of doctors would agree to prescribe marijuana-based medications to a cancer patient in need.
There is, after all, no consensus on the effects of long-term medical and recreational marijuana use. The authors of a review publication, even included in the Cochrane review database (a sort of supreme court in the world of evidence-based medicine), state that a slight decrease in cognitive ability has been observed in marijuana users.
On the other hand, you can read in the article's conclusions that no antipsychotic effect was found by scientists when marijuana was used medically. Toward the end, the researchers refer to the fact that there are not enough clinical studies to meet all the requirements of evidence at this time. But an Anglo-Canadian team of scientists found an increased likelihood of depression in cannabis users.
And how is one of the most common and controversial drugs out there, marijuana? Struggling: With the help of evidence-based medicine, marijuana is trying to carve out its own small patch of use in the therapy of various diseases.
The aforementioned Rick Doblin was one of the first to conduct a rigorous, systematic study that justified the use of marijuana and marijuana-based medicinal forms: they help prevent vomiting and nausea in cancer patients.
The article, published back in 1991 in the authoritative medical journal Journal of Clinical Oncology, ended with the following conclusions: about half of oncologists in one form or another recommended their patients to use marijuana to relieve their symptoms. The same percentage of doctors would agree to prescribe marijuana-based medications to a cancer patient in need.
There is, after all, no consensus on the effects of long-term medical and recreational marijuana use. The authors of a review publication, even included in the Cochrane review database (a sort of supreme court in the world of evidence-based medicine), state that a slight decrease in cognitive ability has been observed in marijuana users.
On the other hand, you can read in the article's conclusions that no antipsychotic effect was found by scientists when marijuana was used medically. Toward the end, the researchers refer to the fact that there are not enough clinical studies to meet all the requirements of evidence at this time. But an Anglo-Canadian team of scientists found an increased likelihood of depression in cannabis users.
So, even among medical professionals there is an ongoing debate about the effects of long-term use of marijuana and marijuana-based medicines. Despite this, in the United States, dronabinol (aka marinol), a synthetic mixture of substances contained in marijuana, is used to treat HIV-mediated anorexia and for maintenance therapy in cancer patients.
So what's the bottom line? What are the effects of marijuana that can be used in medicine?
Cannabinoids have quite strong anti-inflammatory and anti-rheumatoid effects.
Research on the treatment of such diseases is conducted at the University of Aalborg, Denmark, and the Queen Elizabeth II Health Sciences Centre in Halifax, Canada.
The anti-inflammatory effects of marijuana have also been questioned by some teams of scientists. Studies have shown that its main active ingredient, THC, on the contrary, increases the activity of an enzyme involved in the production of pro-inflammatory factors. By the way, this same mechanism can also reduce cognitive abilities in marijuana users.
The clinically significant anti-rheumatoid effect of marijuana has been proven, but its mechanisms are still not entirely clear.
In humans, there are several biochemical pathways that can be active in inflammation, and which one is affected by THC in a way that completely quenches this pathological process is not entirely clear.
What else to read on the subject:
In humans, there are several biochemical pathways that can be active in inflammation, and which one is affected by THC in a way that completely quenches this pathological process is not entirely clear.
What else to read on the subject:
- Moustafa A, Salama M, Peak R, Tindle R, Salem A, Keri S, Mohamed W. (2017). Interactions between cannabis and schizophrenia in humans and rodents - this is a rather detailed literature review, highlighting the blind spots of research on the possible connection between cannabinoid use and the development of schizophrenia. For example, it explicitly points out that to date, there are simultaneous studies proving with equal rigor both an exacerbation of the productive symptoms of schizophrenia (delirium, hallucinations) and no effect on this side of the disease. Interestingly, the situation with negative symptomatology (catatonia, apathy) is similar: there are publications both confirming and denying this point. However, summarizing the data from many clinical studies, the authors of the review still tend to believe that cannabis use is a risk factor for mental illness.
- Ian Hamilton. Cannabis, psychosis and schizophrenia: unravelling a complex interaction (2017) - another perspective on the problem of the connection between marijuana use and mental disorders. Professor Ian Hamilton of York University believes that the propensity to use cannabis is, on the contrary, a protective reaction to stress.
- Ortiz-Medina M, Perea M, Torales J, Ventriglio A, Vitrani G, Aguilar L, Roncero C. Cannabis consumption and psychosis or schizophrenia development (2018) - another perspective on the possible connection between marijuana use and mental disorders can be illustrated by a study which states that marijuana doubles the risk of psychosis only in people who are initially prone to it.