A BRIEF HISTORY OF DISSOCIATIVE DRUGS
Abstract:
Dissociatives are a class of psychoactive drugs with varied uses both within and outside medical context. This article explores a brief summary of their history, uses, and some of the questions these fascinating drugs evoke.
The Primordial Dissociative
Since before the dawn of recorded history, a psychoactive drug was discovered which might well have been the very first drug used by mankind. It was discovered that sugary and starchy foods, if left to spoil, tended to be transformed by the ubiquitous microscopic fungi of the yeast families to a substance later purified and named ethyl alcohol, or "Alcohol". It may in fact have been discovered by observing animals, as for instance elephants deliberately consume overripe fruits, letting them ripen to the point of spoiling, in order to experience the intoxication. This substance, when ingested, gave an effect that amounted to the selective shutting down of parts of the brain, leading to euphoria, merriment and enhanced emotion, enhanced inspiration and a tendency to reminiscing. It was discovered that some of the solids forming in fermenting sugary solutions were the substance that catalyzed the transformation of the food to the drug, and with that discovery the craft of brewing came into being, the craft of selectively letting foods spoil in order to make them contain the drug with a minimum of ill making and ill tasting contaminants. Later Arabic scientists discovered that by heating the mixture and catching the first vapors they could increase the concentration of the drug within the mixture, so that smaller volumes could hold higher intoxicating power and moreover that the drug was so concentrated that it prevented its own spoiling by intoxicating microorganisms to the point they could no longer survive. An essence created by destillation was called Al Kuhl in Arabic, and this entered the English language as "Alcohol of wine", and later, simply, Alcohol.
Alcohol in the brain causes several, but especially two specific effects, one being agonism of the neurotransmitter GABA and the other being, antagonism of the neurotransmitter NMDA. Both of these effects have a strong inhibiting effect on brain activity. Drugs that are primarily GABA agonists are primarily sedatives, while drugs that are primarily NMDA antagonists are "dissociatives", which are the subject of this article.
In olden times there were two major forces acting upon mankind, that of Religion and that of Medicine. Doctors at the time discovered alcohol in large doses could render their patient indifferent to pain and used it as an Anesthetic, a numbing drug that aids painful medical procedures such as setting a dislocated joint or removing a severely damaged limb. It was far from perfect for this purpose, because a dose of alcohol that would render a patient unconscious would, because of the predominant GABA-agonist effects, bring the patient dangerously close to dying. The unconsciousness caused by GABA agonists was much more toxic than that produced by NMDA antagonists in that combination. But, at the time it was the best they had so they made due.
In one of the predominant Religions, Christianity, the primary prophet Jesus was said to have turned water into wine, in order for a celebration to be more proper than one that went without it, and with that he encouraged moderate intoxication while the religion strongly warned against excessive intake or, "drunkenness", which would eclipse the beneficial effects. Shortly before his death he even declared wine, the contemporary form of alcohol, to be a sacrament, likening it to be his blood, offering it to drink to his disciples in rememberance of him, and instructing them to remain doing this. He said the next wine he would drink with them would be in the non-physical realm called Heaven where they would meet with them after their death and remain with them for all eternity.
The Anesthetic revolution
Centuries passed, until a philosopher-scientist Joseph Priestly dampened iron filings with nitric acid and heated it, producing a gas which he purified and called phlogisticated nitrous air. Later this was to be named "Nitrous oxide". Intrepid scientists repeated the experiment and decided to breathe the gas, and it was found that it did not support life without air admixture, but that it did produce a profound and most unusual intoxication. Within seconds after inhaling people would experience highly peculiar experiences that deviated greatly from consensus reality and, because of this, started acting in a most inappropriate manner. This bizarre behavior invoked laughter in spectators and because of that the gas became known informally as "Laughing Gas".
Before long Laughing Gas was used at demonstrations to promote the marvels of science, it was prepared with much bravado from dinitrogen tetroxide and iron filings, purified before the assembled and then bags of it were handed out to spectators who inhaled it, had miraculous experiences of another reality and hilarity ensued. It became a thing of its own and soon the "science denonstration" part moved to the background and indulgence and hilarity regarding nitrous oxide inhalation became the predominant activity of such events.
Nitrous oxide was different from alcohol, it was almost devoid from GABA agonist effects was predominantly active as a NMDA antagonist. It was the first relatively selective Dissociative. Because the consciousness diminishing effects of GABA agonism were gone, the consciousness altering effects of NMDA antagonism became more prominent. Where GABA agonism effected a gradual reduction of consciousness until unconsciousness, NMDA antagonism effected an evermore pronounced alteration and otherworldliness of consciousness, a withdrawal into the self in a world full of experience, until finally consciousness crossed over entirely from the outer realm (consciousness) to the inner realm and unconsciousness resulted. This different mechanism led to dramatically reduced toxicity of anesthetic dosage levels, if care was taken that enough oxygen was mixed in and the unconsciousness didnt last too many hours, it was essentially nontoxic.
This revolutionized anesthesia, as was proven by a dentist with a near painless dental extraction using nitrous oxide. Nitrous oxide began replacing alcohol as an anesthetic, and new anesthetics were sought. For that, people turned to the isolated alcohol molecule. One discovery was to dehydrate it, coupling two alcohol molecules together with loss of a water molecule, creating diethyl ether, or Ether, which had NMDA agonism strongly and GABA agonism less strongly than alcohol, making it more suitable for anesthesia, and another chemist reacted alcohol with chlorinated lime producing a substance called Chloroform, which had enhanced GABA activity and diminished NMDA agonism, which was also less toxic than alcohol, and it too was a viable anesthetic. Ether turned out to produce more bizarre, otherworldly experiences and was relatively less toxic than Chloroform. And Chloroform produced more sedation and was relatively more toxic.
Now surgeons could anesthetize their patients completely without ending up hurting and killing many of them, as was the case with alcohol, and this revolutionized the willingness of patients to undergo drastic surgical procedures. The quest for discovering the perfect anesthetic was on.
Angel Dust
About a century passed when entirely by accident a new drug was created, Phencyclidine which came to be known as PCP or "Angel Dust". A synthesis was conducted to produce a molecule but instead it produced another, it was Phencyclidine. Later on, it was discovered that this compound was very strongly active as a NMDA antagonist and thus had potential as an anesthetic not unlike Nitrous oxide before it. It was developed and used as an anesthetic in humans, but only briefly. PCP was considerably more potent and longer lived than nitrous oxide and patients emerged from their surgery completely taken by experiences they had in an otherworldly realm, behaving in a manner not fitting consensus reality and interacting with a reality that seems alien and distinct from this reality, like in a waking dream with inability to discern between the two, a condition dubbed "psychosis" by the medical profession. While the so called "psychosis" almost always wore off as the drug did, except in some of those prone to spontaneous experiencing of alternate realities, such as schizophrenics, the unprepared patients were quite alarmed to wake up to a reality alien to the one they had lived most of their waking life in, and they were so upsetting to the rest in the post-anesthetic recovery room and staff that PCP was no longer considered a viable human anesthetic. It was subsequently used in anesthesia of large animals but they too emerged from anesthesia engulfed by and interacting with, this otherworldly reality, posing the danger of erratically behaving large animals to the veterinarian and caretakers, so it eventually was dropped from veterinary surgery too. The drugs nonetheless had great potential so the search was on to find better NMDA antagonists for anesthesia and similar medical uses.
At the time, a movement celebrating consciousness altering drugs had started in western society, in emulation of those of most primitive cultures, and PCP began to appear as an intoxicant, used in lower doses not for the sake of anesthesia but to experience the otherworldly realms PCP gives access to. It became known mostly by the name "Angel Dust", referencing again to otherworldly entities related to Christianity, like alcohol before it had been prophesized to be served in the Kingdom of Heaven. Use of Angel Dust became a big trend, that reached its peak in the decade after serotonergic psychedelics peaked, then moved into relative obscurity. PCP was seldom used except in certain African American street subcultures as a preferred intoxicant, and more widespread was the use of a pharmacologically related NMDA antagonist drug, Dextromethorphan, which was developed and available at pharmacies without prescription as a cough suppressant.
Special K
It became fairly quiet around dissociatives for a few decades. Medical science focussed primarily on anesthetics of the Chloroform type, ones that tend to produce diminishment of consciousness leading to unconsciousness, GABA agonism, as opposed to the withdrawal into another realm of consciousness, as produced by NMDA anatagonists. A PCP derivative called Ketamine proved to have a more favorable pharmacological profile and came in use as an anesthetic in emergency medicine, such as on the battlefield, on-site in the aftermath of serious accidents and in the anesthesia of young children and the elderly, for whom GABA agonist anesthetics may be too toxic.
Ketamine saw an upsurge in the consciousness alteration seeking nonmedical subcultures and dubbed "Special K" it became widely used as an intoxicant. In this intensive use a dark side to Ketamine became apparent, its toxic effects on the bladder because of an irritant metabolite leading to permanent damage and even the need for bladder replacement surgery in its most extreme cases.
Memantine
Medical science continued on, looking for medications that exploited the beneficial effects of NMDA antagonists with a minimum of consciousness disruption and the least potential for non-medical use. One such drug is Memantine, currently un use as a daily medication to slow and psychologically ease the progression of Alzheimer's Dementia, but which also finds off-label use for treatment of a staggering range of conditions and disorders, including but not limited to: generalized anxiety disorder, epilepsy, opioid dependence, systemic lupus erythematosus, depression, bipolar disorder, obsessive compulsive disorder, Tourette Syndrome, problem gambling, attention-deficit hyperactivity disorder, glaucoma, tinnitus, neuropathic pain including Complex Regional Pain Syndrome, pervasive developmental disorders, HIV associated dementia, nystagmus, multiple sclerosis, autism, migraine, amyotrophic lateral sclerosis, Down syndrome and for protection of cognitive function during whole brain radiation, showing the trememdous and widespread scope of the promise Dissociative drugs hold for medicine.
Methoxetamine
In the mean time, the non-medical establishment has not sat still, and while the medical establishment searches for a NMDA antagonist with a minimum of the experiencing of the otherworldly reality dissociatives give access to, the consciousness alteration seeking subculture, aided by the advance of science has begun the quest for development of a NMDA antagonist which optimizes the experiencing of this otherworldly reality, with a minimum of toxic side effects, such as Ketamine bladder toxicity, and a minimum of harmful side effects upon the susceptible, such as psychosis enhancing effects in those susceptible to spontaneous experiencing of otherworldly realities. The first prominent one of these came in 2010 with the development of Methoxetamine, the first successful dissociative drug designed and developed outside of the scientific and medical establishment for the expressed purpose of creating an optimized intoxicant since the discovery of alcohol, and with that, for now, a brief history of dissociative drugs comes full circle.
The Elephant In The Room
Reading this, the big question that emerges is: What is this otherworldly realm of consciousness evoked by the usage of dissociatives. Is it the realm of dreams, is it the realms of delirium or psychosis or is it a different realm entirely? What we know, is that usage of NMDA antagonists has inhibiting effects on the sensory perception of consensus reality, and that as this sense diminishes, it is replaced with perception of an entirely different realm. A realm where fantasy and reality mingle into one, a realm that may evoke strong emotion or a complete absence of emotion. A realm that tends to lead to profound inner peace but also great turmoil. A realm which overflows with experiences perceived as "as real as consensus reality" or even more so and which often gives rise to profound spiritual experiences. A realm which the main prophet of Christianity linked with its "Kingdom of Heaven", a realm that makes people behave and think according to a logic that is entirely consistent in that reality but not in the earthly reality. It is without a doubt a realm that exists within us, and one that can be accessed by shutting off the senses, either by taking a dissociative drug, or by floating in a tank of body temperature water, quite like the womb, in silence and darkness. Why needs there be another reality to displace consensus reality when it recedes? Will it be science, or religion to supply us with the answers or must we find our own answers, looking within, shutting off the senses as we connect with that which appears as Divine?
This article was conceived and written under the influence of Methoxetamine.
I hope you enjoyed it, and that it gave you answers and questions to ponder.
Abstract:
Dissociatives are a class of psychoactive drugs with varied uses both within and outside medical context. This article explores a brief summary of their history, uses, and some of the questions these fascinating drugs evoke.
The Primordial Dissociative
Since before the dawn of recorded history, a psychoactive drug was discovered which might well have been the very first drug used by mankind. It was discovered that sugary and starchy foods, if left to spoil, tended to be transformed by the ubiquitous microscopic fungi of the yeast families to a substance later purified and named ethyl alcohol, or "Alcohol". It may in fact have been discovered by observing animals, as for instance elephants deliberately consume overripe fruits, letting them ripen to the point of spoiling, in order to experience the intoxication. This substance, when ingested, gave an effect that amounted to the selective shutting down of parts of the brain, leading to euphoria, merriment and enhanced emotion, enhanced inspiration and a tendency to reminiscing. It was discovered that some of the solids forming in fermenting sugary solutions were the substance that catalyzed the transformation of the food to the drug, and with that discovery the craft of brewing came into being, the craft of selectively letting foods spoil in order to make them contain the drug with a minimum of ill making and ill tasting contaminants. Later Arabic scientists discovered that by heating the mixture and catching the first vapors they could increase the concentration of the drug within the mixture, so that smaller volumes could hold higher intoxicating power and moreover that the drug was so concentrated that it prevented its own spoiling by intoxicating microorganisms to the point they could no longer survive. An essence created by destillation was called Al Kuhl in Arabic, and this entered the English language as "Alcohol of wine", and later, simply, Alcohol.
Alcohol in the brain causes several, but especially two specific effects, one being agonism of the neurotransmitter GABA and the other being, antagonism of the neurotransmitter NMDA. Both of these effects have a strong inhibiting effect on brain activity. Drugs that are primarily GABA agonists are primarily sedatives, while drugs that are primarily NMDA antagonists are "dissociatives", which are the subject of this article.
In olden times there were two major forces acting upon mankind, that of Religion and that of Medicine. Doctors at the time discovered alcohol in large doses could render their patient indifferent to pain and used it as an Anesthetic, a numbing drug that aids painful medical procedures such as setting a dislocated joint or removing a severely damaged limb. It was far from perfect for this purpose, because a dose of alcohol that would render a patient unconscious would, because of the predominant GABA-agonist effects, bring the patient dangerously close to dying. The unconsciousness caused by GABA agonists was much more toxic than that produced by NMDA antagonists in that combination. But, at the time it was the best they had so they made due.
In one of the predominant Religions, Christianity, the primary prophet Jesus was said to have turned water into wine, in order for a celebration to be more proper than one that went without it, and with that he encouraged moderate intoxication while the religion strongly warned against excessive intake or, "drunkenness", which would eclipse the beneficial effects. Shortly before his death he even declared wine, the contemporary form of alcohol, to be a sacrament, likening it to be his blood, offering it to drink to his disciples in rememberance of him, and instructing them to remain doing this. He said the next wine he would drink with them would be in the non-physical realm called Heaven where they would meet with them after their death and remain with them for all eternity.
The Anesthetic revolution
Centuries passed, until a philosopher-scientist Joseph Priestly dampened iron filings with nitric acid and heated it, producing a gas which he purified and called phlogisticated nitrous air. Later this was to be named "Nitrous oxide". Intrepid scientists repeated the experiment and decided to breathe the gas, and it was found that it did not support life without air admixture, but that it did produce a profound and most unusual intoxication. Within seconds after inhaling people would experience highly peculiar experiences that deviated greatly from consensus reality and, because of this, started acting in a most inappropriate manner. This bizarre behavior invoked laughter in spectators and because of that the gas became known informally as "Laughing Gas".
Before long Laughing Gas was used at demonstrations to promote the marvels of science, it was prepared with much bravado from dinitrogen tetroxide and iron filings, purified before the assembled and then bags of it were handed out to spectators who inhaled it, had miraculous experiences of another reality and hilarity ensued. It became a thing of its own and soon the "science denonstration" part moved to the background and indulgence and hilarity regarding nitrous oxide inhalation became the predominant activity of such events.
Nitrous oxide was different from alcohol, it was almost devoid from GABA agonist effects was predominantly active as a NMDA antagonist. It was the first relatively selective Dissociative. Because the consciousness diminishing effects of GABA agonism were gone, the consciousness altering effects of NMDA antagonism became more prominent. Where GABA agonism effected a gradual reduction of consciousness until unconsciousness, NMDA antagonism effected an evermore pronounced alteration and otherworldliness of consciousness, a withdrawal into the self in a world full of experience, until finally consciousness crossed over entirely from the outer realm (consciousness) to the inner realm and unconsciousness resulted. This different mechanism led to dramatically reduced toxicity of anesthetic dosage levels, if care was taken that enough oxygen was mixed in and the unconsciousness didnt last too many hours, it was essentially nontoxic.
This revolutionized anesthesia, as was proven by a dentist with a near painless dental extraction using nitrous oxide. Nitrous oxide began replacing alcohol as an anesthetic, and new anesthetics were sought. For that, people turned to the isolated alcohol molecule. One discovery was to dehydrate it, coupling two alcohol molecules together with loss of a water molecule, creating diethyl ether, or Ether, which had NMDA agonism strongly and GABA agonism less strongly than alcohol, making it more suitable for anesthesia, and another chemist reacted alcohol with chlorinated lime producing a substance called Chloroform, which had enhanced GABA activity and diminished NMDA agonism, which was also less toxic than alcohol, and it too was a viable anesthetic. Ether turned out to produce more bizarre, otherworldly experiences and was relatively less toxic than Chloroform. And Chloroform produced more sedation and was relatively more toxic.
Now surgeons could anesthetize their patients completely without ending up hurting and killing many of them, as was the case with alcohol, and this revolutionized the willingness of patients to undergo drastic surgical procedures. The quest for discovering the perfect anesthetic was on.
Angel Dust
About a century passed when entirely by accident a new drug was created, Phencyclidine which came to be known as PCP or "Angel Dust". A synthesis was conducted to produce a molecule but instead it produced another, it was Phencyclidine. Later on, it was discovered that this compound was very strongly active as a NMDA antagonist and thus had potential as an anesthetic not unlike Nitrous oxide before it. It was developed and used as an anesthetic in humans, but only briefly. PCP was considerably more potent and longer lived than nitrous oxide and patients emerged from their surgery completely taken by experiences they had in an otherworldly realm, behaving in a manner not fitting consensus reality and interacting with a reality that seems alien and distinct from this reality, like in a waking dream with inability to discern between the two, a condition dubbed "psychosis" by the medical profession. While the so called "psychosis" almost always wore off as the drug did, except in some of those prone to spontaneous experiencing of alternate realities, such as schizophrenics, the unprepared patients were quite alarmed to wake up to a reality alien to the one they had lived most of their waking life in, and they were so upsetting to the rest in the post-anesthetic recovery room and staff that PCP was no longer considered a viable human anesthetic. It was subsequently used in anesthesia of large animals but they too emerged from anesthesia engulfed by and interacting with, this otherworldly reality, posing the danger of erratically behaving large animals to the veterinarian and caretakers, so it eventually was dropped from veterinary surgery too. The drugs nonetheless had great potential so the search was on to find better NMDA antagonists for anesthesia and similar medical uses.
At the time, a movement celebrating consciousness altering drugs had started in western society, in emulation of those of most primitive cultures, and PCP began to appear as an intoxicant, used in lower doses not for the sake of anesthesia but to experience the otherworldly realms PCP gives access to. It became known mostly by the name "Angel Dust", referencing again to otherworldly entities related to Christianity, like alcohol before it had been prophesized to be served in the Kingdom of Heaven. Use of Angel Dust became a big trend, that reached its peak in the decade after serotonergic psychedelics peaked, then moved into relative obscurity. PCP was seldom used except in certain African American street subcultures as a preferred intoxicant, and more widespread was the use of a pharmacologically related NMDA antagonist drug, Dextromethorphan, which was developed and available at pharmacies without prescription as a cough suppressant.
Special K
It became fairly quiet around dissociatives for a few decades. Medical science focussed primarily on anesthetics of the Chloroform type, ones that tend to produce diminishment of consciousness leading to unconsciousness, GABA agonism, as opposed to the withdrawal into another realm of consciousness, as produced by NMDA anatagonists. A PCP derivative called Ketamine proved to have a more favorable pharmacological profile and came in use as an anesthetic in emergency medicine, such as on the battlefield, on-site in the aftermath of serious accidents and in the anesthesia of young children and the elderly, for whom GABA agonist anesthetics may be too toxic.
Ketamine saw an upsurge in the consciousness alteration seeking nonmedical subcultures and dubbed "Special K" it became widely used as an intoxicant. In this intensive use a dark side to Ketamine became apparent, its toxic effects on the bladder because of an irritant metabolite leading to permanent damage and even the need for bladder replacement surgery in its most extreme cases.
Memantine
Medical science continued on, looking for medications that exploited the beneficial effects of NMDA antagonists with a minimum of consciousness disruption and the least potential for non-medical use. One such drug is Memantine, currently un use as a daily medication to slow and psychologically ease the progression of Alzheimer's Dementia, but which also finds off-label use for treatment of a staggering range of conditions and disorders, including but not limited to: generalized anxiety disorder, epilepsy, opioid dependence, systemic lupus erythematosus, depression, bipolar disorder, obsessive compulsive disorder, Tourette Syndrome, problem gambling, attention-deficit hyperactivity disorder, glaucoma, tinnitus, neuropathic pain including Complex Regional Pain Syndrome, pervasive developmental disorders, HIV associated dementia, nystagmus, multiple sclerosis, autism, migraine, amyotrophic lateral sclerosis, Down syndrome and for protection of cognitive function during whole brain radiation, showing the trememdous and widespread scope of the promise Dissociative drugs hold for medicine.
Methoxetamine
In the mean time, the non-medical establishment has not sat still, and while the medical establishment searches for a NMDA antagonist with a minimum of the experiencing of the otherworldly reality dissociatives give access to, the consciousness alteration seeking subculture, aided by the advance of science has begun the quest for development of a NMDA antagonist which optimizes the experiencing of this otherworldly reality, with a minimum of toxic side effects, such as Ketamine bladder toxicity, and a minimum of harmful side effects upon the susceptible, such as psychosis enhancing effects in those susceptible to spontaneous experiencing of otherworldly realities. The first prominent one of these came in 2010 with the development of Methoxetamine, the first successful dissociative drug designed and developed outside of the scientific and medical establishment for the expressed purpose of creating an optimized intoxicant since the discovery of alcohol, and with that, for now, a brief history of dissociative drugs comes full circle.
The Elephant In The Room
Reading this, the big question that emerges is: What is this otherworldly realm of consciousness evoked by the usage of dissociatives. Is it the realm of dreams, is it the realms of delirium or psychosis or is it a different realm entirely? What we know, is that usage of NMDA antagonists has inhibiting effects on the sensory perception of consensus reality, and that as this sense diminishes, it is replaced with perception of an entirely different realm. A realm where fantasy and reality mingle into one, a realm that may evoke strong emotion or a complete absence of emotion. A realm that tends to lead to profound inner peace but also great turmoil. A realm which overflows with experiences perceived as "as real as consensus reality" or even more so and which often gives rise to profound spiritual experiences. A realm which the main prophet of Christianity linked with its "Kingdom of Heaven", a realm that makes people behave and think according to a logic that is entirely consistent in that reality but not in the earthly reality. It is without a doubt a realm that exists within us, and one that can be accessed by shutting off the senses, either by taking a dissociative drug, or by floating in a tank of body temperature water, quite like the womb, in silence and darkness. Why needs there be another reality to displace consensus reality when it recedes? Will it be science, or religion to supply us with the answers or must we find our own answers, looking within, shutting off the senses as we connect with that which appears as Divine?
This article was conceived and written under the influence of Methoxetamine.
I hope you enjoyed it, and that it gave you answers and questions to ponder.
![:\](https://bluelight.org/xf/BL_Images/Orig_Emoji/wrygrin.gif "wry grin :\")
