David E Nichols and a Primer on Hallucinogens

David E Nichols previously held the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology at Purdue University and is considered to be one of the world’s leading experts on hallucinogens. His excellent 2004 review of the literature, “Hallucinogens”, discusses a breadth of topics, including history, pharmacology, toxicity, addictiveness and psychological outcomes.


Courtesy Mario Martinez (aka MARS-1)

However, it is a long paper and many may struggle with its scientific content. Because of this, what follows is a short primer designed to introduce readers to some of the key concepts contained within this paper. Please be aware that this is simply a commentary on Nichols’ work and he has not authorised my interpretation, or had anything to do with its preparation.

This primer was initially written to be sent to Victorian politicians in support of the campaign to obtain regulated access for spiritual and religious purposes. Because of this, there are a number of references to this type of use within.

It is important to note that rather than address all hallucinogens (aka psychedelics), Nichols focuses on the three classical hallucinogens (which also happen to be Transcendent Compounds): LSD, Psilocybin and Mescaline.

“Hallucinogens, for the purposes of this review, will mean only substances with psychopharmacology resembling that of the natural products mescaline and psilocybin and the semisynthetic substance known as lysergic acid diethylamide (LSD-25).” (p 132)

One of the issues that often confounds people unfamiliar with the safety of these compounds is the obvious fact that they have been rendered illegal the world over. Surely, this must mean that there is something wrong with them? Nichols addresses the discrepancy between the safety of these compounds and the reactions to them by government and law enforcement saying:

“Despite their high degree of physiological safety and lack of dependence liability, hallucinogens have been branded by law enforcement officials as among the most dangerous drugs that exist, being placed into Schedule I of the Controlled Substances Act. Depending on the locale, especially in the United States, punishments for using or distributing drugs like LSD are often more draconian than if the user had committed a violent crime.” (p 133)

Furthermore, when faced with the question of “What is it, exactly, that makes these pharmacological curiosities so fearsome?” Nichols surmises that:

“The answer lies, in large measure, beyond hard science and within a complex sociological and political agenda that surround psychedelics” (p 133)

At the risk of putting words into the mouth of such an esteemed researcher, I would suggest that this translates to the assertion that it is politics, rather than science that is responsible for these compounds being treated as they are. That if only the politicians and bureaucrats paid attention to the science, these “pharmacological curiosities” would assume a far less fearsome aspect and could be treated with the respect they deserve and that legislation and regulation would reflect them as they are, rather than the demons that some wish them to be.

But what of the “hard science”? What does it actually have to say?
With respect to the toxicity of these compounds, Nichols is quite clear when he says:

“Hallucinogens are generally considered to be physiologically safe molecules whose principal effects are on consciousness. That is, hallucinogens are powerful in producing altered states of consciousness (ASC), but they do so at doses that are not toxic to mammalian organ systems. There is no evidence that any of the hallucinogens, even the very powerful semisynthetic LSD, causes damage to any human body organ.” (p 134)

Furthermore, with respect to long-term adverse physiological effects arising from their use, he notes that:

“Strassman (1984) and Halpern and Pope (1999) have analyzed the published reports on adverse reactions and negative long-term sequelae following hallucinogen use. Halpern and Pope reached a conclusion similar to Strassman’s earlier analysis that concerning repeated use of psychedelic drugs the results were controversial, but if any long-term adverse effect did occur it was ‘‘subtle or nonsignificant.’’ It should be noted, however, that in both studies their conclusions were specifically developed based on reviews of supervised clinical research with hallucinogens.” (p 134)

While Nichols qualifies his statement by indicating that these conclusions were based on supervised clinical research, I should note that I am not aware of any research indicating problematic sequelae for populations that have used this compound outside of supervised clinical research (Indeed recent research has shown quite the reverse). This apparent safety is a highly important observation, given that there exists an entire cohort within the community who have been using this compound for in excess of fifty years and who would be easily identifiable as being burdened with Hallucinogen induced disease if it actually existed.

Moving onto the issue of addiction he says:

“In contrast to many other abused drugs, hallucinogens do not engender drug dependence or addiction and are not considered to be reinforcing substances” (p 134);

“There are no literature reports of successful attempts to train animals to self-administer classical hallucinogens, an animal model predictive of abuse liability, indicating that these substances do not possess the necessary pharmacology to either initiate or maintain dependence.” (p 134);

“hallucinogens do not produce the type of reinforcing effects that occur after use of substances such as cocaine or amphetamine” (p 138)

Nichols also notes that because these compounds do not produce the cravings associated with other drugs, their usage pattern is markedly different:

“It must be kept in mind that hallucinogen use is generally not compulsive and long lasting and that these substances do not produce dependence. Their use is more often episodic, and most people do not continue to use hallucinogens on a long-term basis after some initial experimentation. Surveys have shown that hallucinogen use is most likely to occur in the late teens and into the early 20s but does not usually continue after users reach their late 20s (Chilcoat & Schutz, 1996). Chronic use of hallucinogens is unusual (Henderson, 1994; Chilcoat & Schutz, 1996). This use pattern is in distinct contrast to the compulsive abuse that is often seen with rewarding drugs such as amphetamines, cocaine, or the opiates, which produce craving.” (p 138)

This pattern of usage matches the observations of myself and others within the broader Australian “Entheogenic” community. It is not uncommon for people to move into the community for a couple of years, obtain what gifts they feel the compounds had to offer, before moving back out into the normal community and rarely if ever using these compounds again.

But while chronic (i.e. long-term) use might be comparatively rare, it is these users, such as myself, who form the backbone of the longer term community of users and provide continuity, depth and wisdom that is arguably lacking among most other subcultures of substance users. Certainly my motivations for use, along with many others, whom it is my privilege to know, would agree with the following statement:

“When asked why they use hallucinogens, individuals who take doses with significant psychological effects often say that they use them for personal or spiritual development and increased understanding and self-discovery, that their use seems important to them, and that often they feel they gain important personal, religious, or philosophical insights.” (p 138)

Nichols is not afraid to address the potential negatives of the use of hallucinogens.

One of the more commonly stated concerns with the use of these compounds is the phenomena known as “flashbacks”. Nichols addresses this by saying:

“One adverse consequence of hallucinogen use is known as ‘‘flashbacks.’’ Flashbacks were widely discussed in the press, particularly in earlier decades, as one of the most common adverse effects of hallucinogens; their occurrence was emphasized as a deterrent to recreational use. A flashback essentially consists of the re-experiencing of one or more of the perceptual effects that were induced by hallucinogens but occurring after the effect of the drug has worn off or at some later time in the complete absence of the drug. Flashbacks most often appear as visual symptoms and can persist for months or in some cases years, and there appears to be no relationship between frequency of hallucinogen use and rate of occurrence.” (p 135)


“Based on the millions of people who have taken hallucinogens, the incidence of HPPD appears to be very small, and there is presently no effective treatment.” (p 135).

I would make two observations here. Firstly, while it is unfortunate that there are a “very small” number of people who experience difficulty with flashbacks, it is doubtful whether the fact that there are potential dangers inherent to an activity is grounds for making that activity illegal. If that were the case, we’d be banning origami on the basis of paper cuts. Secondly, even while acknowledging the risks inherent in the phenomenon of flashbacks, a reasonable person is still going to be forced to conclude that these compounds are immeasurably safer than the only current legal alternative, alcohol. The UN reports that 5.9% of all deaths (3.3 million) in 2012 were attributable to alcohol so it isn’t hard to imagine why the adoption of hallucinogen use in preference to alcohol  would be beneficial to the wider community.

Importantly, with respect to the aims of the current paper, Nichols points out that research indicated that:

“when LSD was used in a therapeutic or research setting, HPPD appeared less frequently than when it was used recreationally.” (p 135)

This is important, as very few people are arguing for wide-ranging and unregulated access to the compounds, but rather to ensure their availability for religious, sacramental and safe recreational use.

Within the context of my own campaign for regulated access for religious and spiritual purposes, I would suggest that usage would be expected to fall somewhere in-between those of purely recreational and purely therapeutic users. As such, the already “very small” incidence of flashbacks would be reduced even further within a population using these compounds for religious purposes.

Nichols also addresses the issue of physical danger arising from the use of these compounds, particularly in unsupervised settings.

“There are, however, real and significant dangers that can accompany recreational use of these substances. Although LSD or other classical hallucinogens have not directly caused overdose death… (p 135)

Nichols is perhaps incorrect when he says that “hallucinogens have not directly caused overdose death”. There has been precisely one journal article describing the death of a person by LSD overdose. The 1985 article “A Fatal Overdose With LSD”, provides toxicology results for a man who died 16 hours after being admitted to hospital and whose death was determined by the coroner to be due to “LSD poisoning”.

This paper is significantly flawed as it contains no indication of the amount initially consumed, or the time between consumption and eventual death. While there is no data that might allow the calculation of precisely how much LSD might be required for an overdose, the amount is generally held to be at least 1000 times the active dose, which compares well to 10 times the active dose for alcohol.

In any case, a single fatal overdose involving classical hallucinogens after more than 70 years of use by millions of people is a tribute to the inherent safety of the compound. Only the most devious or dishonest could characterise it as being “deadly” in any meaningful sense.

Nichols continues:

…fatal accidents during LSD intoxication have occurred (Jaffe, 1985). This danger is significant, particularly when these drugs are used recreationally in unsupervised settings. Belief that one has superhuman powers while judgment is impaired by hallucinogens can lead to injury or death when an unsupervised user carries out dangerous activities such as walking out on a freeway or attempting to fly (see, e.g., Reynolds & Jindrich, 1985). (p 135)

Accidents will happen, irrespective of whether people are using mind altering substances, or not. Undoubtedly accidents are more frequent when mind altering substances of any sort are consumed. However, insisting that Transcendent Compounds alone are banned on the strength of this argument is untenable, especially given the overwhelming number of alcohol induced accidents and the lack of concern and action that this has generated in government circles.

Although not mentioned by Nichols, the potential for drug driving is a legitimate and real concern, but again is mirrored by the scourge that alcohol has been on our roads even since the days of the horse and buggy. While it can be regarded as certain that an increase in availability of Transcendent Compounds would result in an increase in motor accidents as a result of their inappropriate use, Any government putting this forward as a reason for maintaining full prohibition, while not similarly legislating to ban alcohol is at the very least acting in a duplicitous and hypocritical manner.

Within the context of spiritual and religious use, one could perhaps expect usage within a more controlled environment and it would be expected that this would greatly curtail the potential for drug driving.

It is intriguing that Nichols mentions people “attempting to fly” while on LSD. This has been a recurrent theme among LSD scare-mongers ever since the death of Diane Linkletter in October of 1969 and can arguably be traced back to a scene in the now infamous 1938 anti-cannabis movie “Reefer Madness”. Fortunately, it seems that this particular concern is one that has been greatly blown out of proportion. This story can be considered to have been well debunked by the highly regarded “urban myth” web site, snopes.com, where they not only point out that the girl was certainly not on LSD at the time of her death, but that there was never any evidence beyond hearsay to say that she had ever taken the compound.

The Reynolds & Jindrich article referenced by Nichols is one that I have yet to get my hands on, but it apparently describes a person who ran off a cliff and fell to their death under the influence of Mescaline. While it might be the case that this person believed that he might be able to fly while under the influence of this compound, a single incident is hardly indicative of a wider tendency. It can be argued that people believe all sorts of silly things while under the influence of all sorts of drugs, and one should not discount the possibility of people believing that they can fly while using hallucinogens. But given the breadth of use, it is disappointing when isolated incidences are presented as if they are global trends towards self-destruction.

“Less serious but still very substantial injuries can occur in unusual ways. For example, severe and irreversible ocular damage has resulted from prolonged staring at the sun by individuals under the influence of LSD (Schatz & Mendelblatt, 1973; Fuller, 1976).” (p 135)

We can see a similar situation in when discussing the supposed phenomena of people looking into the sun while under the influence of LSD. Once again, snopes.com has debunked this particular myth, which they describe as being, “one of the 1960s most ubiquitous pieces of drug scarelore”.

While I was unable to obtain the Schatz & Mendelblatt article referenced by Nichols, examining Fuller (1976) is quite educational. It includes the case studies of two patients, both of whom appear to have been suffering from significant mental health issues, with the first patient being formally diagnosed as suffering from “paranoid schizophrenia”.

The situation with the second patient is in itself quite intriguing and deserves to be quoted directly:

“Case 2, a 15-year-old Caucasian female, heard a lecture at her public high school warning of the harmful effects of the illicit use of drugs. The lecturer told the audience that one could sustain a retinal burn with loss of vision if one gazed at the sun while under the influence of hallucinogenic drugs. The patient thought that “it would be a neat thing to burn out my retinas”. She then proceeded to take LSD, having taken it “a few times before”, and stared at the sun for an unknown length of time.”

Rather than a mishap caused by the consumption of LSD, this appears to be a classic example of the self-fulfilling prophecy. With tragic irony, she was subjected to a lecture on the dangers of drugs that included the scarelore myth that people burn their eyes out by staring into the sun while on LSD. As a result of this lecture, she proceeded to take LSD with that specific intention in mind, because she thought that “it would be a neat thing to burn out my retinas”. Rather than being an example of people doing silly things on LSD, this would be more accurately viewed as a classic case of teenage self harm, albeit by very unusual means.

While hardly being an expert on solar retinopathy, I would suggest that its incidence would be comparatively high among people with mental health issues and particularly high among those suffering from schizophrenia and that these cases would be better viewed as the result of mental illness, rather than the consumption of LSD.

My review of the literature was unable to uncover any other incidents of people looking into the sun and damaging their eyes while on LSD, or any of the other Transcendent Compounds. Once again, isolated, if spectacular and attention grabbing incidents are hardly indicative of widespread dangers to either users, or the wider community.

If either attempting to fly, or staring into the sun were a common result from the consumption of classical hallucinogens, there would be far more than a literal handful of cases after decades of ongoing and unsupervised use by perhaps hundreds of millions of people worldwide. Justifying a ban on these compounds because of these incredibly rare kinds of occurrences is akin to banning houses because planes fall on them.

Nichols also addresses the very real concern that these compounds might produce psychosis in individuals. Once again, it is instructive to quote him in detail on this issue.

“The most significant dangers of psychedelics, however, appear to lie principally in their psychological effects. LSD can induce disturbances of experience, otherwise observed only in psychoses, such as alteration of cognitive functions, and depersonalization. Hallucinogens can catalyze the onset of psychosis or depression, which has sometimes led to suicide, and Cohen (1960) has estimated the incidence of LSD-related psychosis to be about 8 per 10,000 subjects. In another study, one case of psychosis was reported in a survey of 247 LSD users (McGlothlin & Arnold, 1971). Fortunately, however, these drugs do not appear to produce illness de novo in otherwise emotionally healthy persons, but these problems seem to be precipitated in predisposed individuals”

One should never arbitrarily discount the potential for harm arising from the use of any compound and it appears that there is the very real risk of psychological harm resulting from the use of these compounds. However, in recognising this and making allowances for it within our legislative frameworks, it should be noted that the occurrence of these negative events is significantly less than one percent and seems to occur only among individuals who are predisposed.

I would suggest that while recognising the dangers is important, so too is recognising that the overwhelmingly vast majority of people using these substances will not encounter these difficulties and that a significant number of people who do will do so regardless of whether their experience is initially bought on by the use of a Transcendent Compound.

If people are going to be using these compounds, then doing so within a religious and spiritual setting, where support networks can more easily be erected around potentially vulnerable people, would be the best way to ensure that those who do suffer adverse impacts from their use and are best able to receive the treatment which they need.

I would also point out that alcohol, which is the only currently legal mind altering substance (I don’t include tobacco, coffee and others, which, while legal aren’t taken to achieve massively mind altered states of consciousness)  has a far worse track record with respect to the mental health of those who use it, with an estimated 10% of users experiencing difficulties with its use and with significant production of illness among people who would have experienced no psychological issues had they refrained from consumption.

While Nichols doesn’t frame his conclusions in these terms, his 2004 peer-reviewed paper “Hallucinogens” makes it quite clear that these substances are non-addictive, non-toxic and psychologically safe. Given this, there can really be no excuse for prohibiting their use for religious and spiritual purposes within the State of Victoria.

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