Lysergic acid diethylamide : a drug of ‘use’ ?

Saibal Das, Preeti Barnwal, Anand Ramasamy, Sumalya Sen and Somnath Mondal

Therapeutic Advances in Psychopharmacology, 2016, Vol. 6, (3), 214–228

DOI: 10.1177/2045125316640440

 

Abstract : Lysergic acid diethylamide (LSD), described as a classical hallucinogen, began its journey from the middle of the last century following an accidental discovery. Since then, it was used as a popular and notorious substance of abuse in various parts of the world. Its beneficial role as an adjunct to psychotherapy was much unknown, until some ‘benevolent’ experiments were carried out over time to explore some of its potential uses. But, many of its effects were unclear and seemed to be a psychedelic enigma. In this review article, we have described the receptor pharmacology, mechanism of action, effects and adverse effects of LSD on the normal body system. We have also highlighted its addictive potentials and the chances of developing tolerance. We have assimilated some of the interesting therapeutic uses of this drug, such as an anti-anxiety agent, a creativity enhancer, a suggestibility enhancer, and a performance enhancer. We have also described LSD to be successfully used in drug and alcohol dependence, and as a part of psychedelic peak therapy in terminally ill patients. The relevant chronological history and literature in the light of present knowledge and scenarios have been discussed. Based on available evidence, LSD could be tried therapeutically in certain specific conditions under controlled settings. But as we mention, due to all the safety concerns, the use of this nonaddictive ‘entheogen’ in actual practice warrants a lot of expertise, caution, cooperation and ethical considerations.

Keywords : abuse, addiction, dependency, hallucinogen, lysergic acid diethylamide, psychedelic

 

Introduction

In its journey from the middle of the last century, lysergic acid diethylamide (LSD) has been used as a popular and notorious substance of abuse globally. Its putative role in psychotherapy was much less understood, until sporadic experiments were carried out over time to explore some of those properties. In this review article, we have highlighted the receptor pharmacology, mechanism of action, effects, adverse effects and addictive potentials of LSD. We have described some of the interesting uses of this drug in psychiatry, such as an anti-anxiety agent, a creativity enhancer, a suggestibility enhancer, a performance enhancer, and also its other successful uses like in drug and alcohol dependence, and as a part of psychedelic peak therapy in terminal illness. We have highlighted the relevant chronological history and literature in the light of present knowledge, and suggest that based on available evidence, LSD could be tried therapeutically in certain specific conditions under appropriate settings.

Effects of LSD on the normal system

LSD has been known over the last century as a remarkable hallucinogenic agent. Albert Hofmann,
who pioneered the invention of LSD, expressed that psychedelics could see its way into the future through transpersonal psychology. He went on to say, ‘It was only through this route of transpersonal
psychology that we could gain access to the spiritual world’ [Grob, 2002, p. 16]. LSD can be termed an ‘entheogen’, which means that the user feels ‘as if the eyes have been cleansed and the person could see the world as new in all respects’ [Ruck et al. 1979, p. 145]. It is said to enhance the user’s appreciation of the environment, and increases creativity. It also seems to ‘open the gates of awareness’ to the mind-bending mystical or religious experiences and overall brings profound changes in the user [Passie et al. 2008].

LSD is one of the most potent, mood-changing, semi-synthetic psychedelic agents, colloquially measured in ‘hits’ or ‘tabs’. Numerous synthetic methods in clandestine laboratories have been used successfully or unsuccessfully to produce this drug. The popular street names are: Acid, Stamp, Lucy, Microdots, Purple Heart, Sunshine, Heavenly Blue, and so on. Its use as a recreational agent started by the early 1960s and popularity continued into the early 1970s.

The effects of LSD are remarkably unpredictable. The effects are due to interruption of the normal interaction between the brain cells and serotonin [Eveloff, 1968]. The usual mental effects are delusions,
visual hallucinations, distortion of sense of time and identity, impaired depth and time perception,
artificial sense of euphoria or certainty, distorted perception of the size and shape of objects, movements, color, sounds, touch and the user’s own body image, severe, terrifying thoughts and feelings, fear of losing control, fear of death, panic attacks, and so on [Liester, 2014].

LSD users often experience loss of appetite, sleeplessness, dry mouth and tremors. Visual changes are among the more common effects; the user can become fixated on the intensity of certain colors. Extreme changes in mood, anywhere from a spaced-out ‘bliss’ to ‘intense terror’, are reported [Eveloff, 1968]. Not only do users disassociate from their usual daily activities, but they also keep taking more drugs in order to re-experience the same [Schmid et al. 2015].

Behavioral and emotional dangers are often pronounced. Severe anxiety, paranoia, and panic attacks occur at high doses and are called ‘bad trips’. Most users express that they had bad trips due to the environment and people surrounding their use [Eveloff, 1968]. Even touch and normal bodily sensations turn into something strange and bizarre. And dangerously, some people never recover from such psychosis. Sensations may seem to ‘cross over’, giving the user the feeling of ‘hearing colors’ and ‘seeing sounds’. These changes can be frightening and can cause panic attacks. Many LSD users experience flashbacks, or a recurrence of the LSD ‘bad trip’, often without warning, even long after taking LSD [Eveloff, 1968; LSD Dangers, 2015]. These effects typically begin within 30–60 min after taking the drug
and can last for up to 12 h [Schmid et al. 2015].

The dosage that is required to produce a moderate effect in most subjects is 1–3 μg/kg body weight. The physical effects produced are: dilated pupils, higher or lower body temperature, sweating or chills, loss of appetite, sleeplessness, dry mouth, tremors, and so on. Stimulation of the sympathetic nervous system can lead to hypothermia, piloerection, tachycardia with palpitation, and elevation of blood pressure and hyperglycemia. These reactions of the autonomic nervous system are not as significant as other effects on the body. Actions on the motor system in the central nervous system lead to increased activity of monosynaptic reflexes, increase in muscle tension, tremors, and muscular incoordination. This latter effect of muscular incoordination is also a symptom of religious ecstasy in many cultures, where the worshipper has such a profound feeling of love of God that he is said to be ‘intoxicated by God’ [Aghajanian and Marek, 1999].

LSD users may manifest relatively long-lasting psychoses or severe depression, and because LSD
accumulates in the body, users develop tolerance. As a result, some repeat users have to take LSD in increasingly higher doses and this increases the physical effects and also the risk of ‘bad trips’. Flashback or a sudden recurrence of the user’s experience can trigger traumatic or strange experiences, even after many hours or months of abstaining from the drug. Schizophrenia and severe depression may also occur with chronic use [Martin, 1970]. These might result from the modulation of serotonin activity by the action of LSD on central 5-HT2A receptors [Steeds et al. 2015; Goldman et al. 2007].

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10.1177_2045125316640440