Drug-induced mental disorders: a common reason for concern?

Most psychoactive drugs alter our cognitive and emotional states, but does chronic use implicate a pathological change in our mental condition?

If we chronically alter transmitter pathways, adaptations will certainly take place. Adaptations are expressed during addiction in sensitization and desensitization of transmitter pathways. This leads to an up- or downregulation of receptors and transporters and eventually to tolerance as well as craving when the drug is withdrawn. These adaptations originate out of natural compensation, but leave former drug users with an imbalanced brain chemistry and an increased risk for several mental disorders. Patients with substance disorders are twice as likely to suffer from mood and anxiety disorders (National Institute on Drug Abuse). Basically, all drugs alter dopaminergic regulation and consequently, our motivation and ability to experience pleasure is changed. Several drugs also cause neurotoxicity and can therefore easily lead to permanent damage, e.g. depression after prolonged ecstasy use due to serotonergic cell death. 
Apart from emotional disturbances, the most common drug-induced illness is psychosis; with alcohol (18%), cannabis (13%) and cocaine (18%) being the most common inducers [1]. One could blame everything on 'high risk drugs', yet, for many mental disorders susceptibility genes have been found, e.g. the VAL/VAL variant of the COMT-gene in cannabis users who go on to develop schizophrenia [2]. Other factors, such as food intake, can severely affect mental outcome after chronic drug use, for example vitamin b12 deficiency in alcoholics, which can lead to several mental disorders, including psychosis and depression.
Hence, aside from chronic substance use, our environmental and genetic conditions play a decisive role in the development of long lasting drug-induced mental pathologies.
  
[1] Drake et al., Am J Psychiatry, 2011
[2] Caspi et al., Biol Psychiatry, 2005

By Anne Schwerk, PhD Alumna, AG Neuronal Regeneration and Plasticity (Dr. med. Barbara Steiner)


This article originally appeared in CNS Volume 5, Issue 1, Mental Health Disorders

Exploring the Mind Through Sacred Plants

In our society, there is amazement surrounding hallucinogens, especially among young people and artists who are curious about mind altering substances. There is a large wave of "psychonauts" that travel far to consume magic mushrooms or other exotic substances; for example, to Latin America, where some of these plants originate, or to countries where consumption is legal (like Uruguay and the Netherlands).

Shamanism Is an Ancient Profession

It is important to underline that in traditional cultures these sacred plants were used for divination and healing purposes. For many indigenous people, psychoactive plants have divine qualities and are used in ceremonies guided by a shaman. A shaman is a practitioner who has expertise with the substance and the wisdom to diagnose and cure soul affections and is believed to have special powers to perceive and interact with the transcendent world [1]. Among such rituals, there are different paradigms: the healer is the one engaging in a trance state to be able to give a diagnosis and apply a remedy. The shaman is the one who guides the persons during the ritual to facilitate self-understanding. The substances might also be consumed during folk religious ceremonies [2]. 

One of the immediate side effects is vomiting, which is believed to aid “purification of the soul”. The desired effect, a spiritual trance, is a complex phenomenon of altered consciousness and usually triggers states of deep introspection and insight. The experience is unique for each consumer but generally depends on the potency of the batch, the setting, the mindset of the user and the culture. The most notable effects are visual alterations that range from seeing visual images and illusions to concrete and substantive hallucinations [3].

source: Wikimedia Commons

The Vine of the Soul

One of the most vastly studied hallucinogens is ayahuasca, a botanical preparation used in healing ceremonies throughout the area of the Amazon in South America. Ayahuasca can be translated from Quechua as “vine of the soul”. The brew includes the ayahuasca vine (Banisteriopsis caapi) containing β-carboline type alkaloids, like harmine and tetrahydroharmine, which are monoamine oxidase (MAO) inhibitors, preventing dopamine breakdown in the synapse; and the chacruna shrub (Psychotria viridis), providing the hallucinogen alkaloid DMT. Sometimes the chacruna shrub is substituted with other plants containing DMT [3, 4]. MAO inhibition and DMT together produce boosted hallucinations, the “magical” effect of this drink [4].

Psychonauts go on trips for ancient plants

There is another important drug for psychonauts: magic mushrooms containing the active compounds of psilocybin, psilocin and baeocystin. They have been part of human culture since prehistoric times (see Image 1). The Aztecs worshiped them to the level that they named them teonanácatl, “the flesh of the god” in nahuatl. The large diversity of mushrooms is used for religious rites by the Mazatec in Oaxaca, Mexico, but also other communities.

The cactus peyote (Lophophora williamsii) was also consumed extensively by the Aztecs, believing it would grant them divine protection and guidance during hunting or warfare. Nowadays, it continues to be used by the Huichol in the desert zone of Real de Catorce in northern Mexico [3]. The members of this tribe depict their ritual gatherings and the hallucinations experienced under the effect of mescaline, the active component of peyote, in extraordinary colorful artistic works (Image 2).

by antefixus21 via flickr 

Where Sacramental Traditions and Neuroscience Meet

Since colonial times, these sacramental plants have largely remained prohibited. However, during the last decades, they have become increasingly known across the Western World, leading to a growing number of research studies that analyze their effects on the brain and their potential clinical value. Now it is known that all these hallucinogenic chemicals have a stereochemical similarity to serotonin. By acting as serotonin receptor agonists, particularly of the frontocortical 5-HT2A subtype [5], they produce alterations of perceptions, mood, and cognition.  

A leading group in this field is the Brazilian team of Dr. Jaime Hallack in the Ribeirão Preto Medical School, University of São Paulo. They have identified promising therapeutic benefits for diseases like depression, anxiety and drug dependence for these substances [6, 7]. Additionally, these medications may have a greater safety profile than regular addictive drugs, an extremely low mortality rate and produce almost no physical dependence [8]. So, if you are a psychonaut or are interested in this topic, keep your eyes wide open, as there is still a great deal to learn from these ancestral sacred plants.

[1] Singh, Behav Brain Sci, 2017 (forthcoming)

[2] Metzner, J Psychoactive Drugs, 1998

[3] Díaz, Phenom Cogn Sci, 2010

[4] Frecska et al., Front Pharmacol, 2016

[5] Dos Santos et al., Neurosci Biobehav Rev, 2016

[6] Dos Santos et al., J Psychopharmacol, 2016

[7] Dos Santos et al., Ther Adv Psychopharmacol, 2016

[8] Winkelman, Curr Drug Abuse Rev, 2014

By Lya Katarina Paas Oliveros, MSc Student MedNeuro

This article originally appeared September 2017 in CNS Volume 10, Issue 3, Spirituality in Science

Psychotropic Substances: An Introductory Journey Through the World of Drugs

Since the beginning of recorded history, people have puzzled about spirituality, and how strong feelings linked to it may be related to forces beyond our control. How can one pin down mystic experience, or life-changing epiphanies? One way is to get down to the nitty-gritty of chemical reactions in the brain. Psychoactive drugs are substances that cause temporary alterations in mood, behavior, perception and consciousness [1]. These substances can be divided according to their origin (synthetic or naturally occurring) and purpose of use, such as medical, recreational or as entheogens for spiritual experiences. 

Drugs affect consciousness differently

The history of psychoactive drugs linked to religious practices use goes back thousands of years to ancient cultures like Mesoamerica or Egypt (see also page 7). Many ancient cultures consumed mostly organic substances for medical purpose, but also in shamanistic rituals to communicate with their gods. Even in some present-day societies, such as some indigenous groups in Mexico or Brazil, this is actively practiced as part of local culture. Throughout history, humans have always been drawn to experimenting with their state of consciousness. This reached a scale that international authorities felt obliged to set up a Convention on Psychotropic Substances, signed by the United Nations in 1971, to rein in the increasing availability of drugs that ‘have negative health effects and lead to lowered moral standards’ [2]. What has changed, however, is people’s motives: as nowadays, people are more likely to use these drugs for fun and improved performance rather than spiritual experience.

Source: Wikipedia Commons

The Pocket Library of Psychoactive Drugs
Whatever the purpose, recreational or religious, the pharmacological effects of psychoactive drugs (and, as a consequence, what they are primarily used for) can vary widely. Below is a concise table of some of the most important substances and their mode of action [2]. It should be noted that the listed licit and illicit drugs often have multiple biological effects, including side effects, which also depend on their dosage.



Moral Remarks
Dr. Timothy Leary, a former leading proponent of hallucinogen use, postulated a theory in the 1960s based on personal experiences [3], in which he stated that the effect of a psychotropic substance on an individual is influenced by the chemical and pharmacological nature of the drug, but also by the individual’s psychological and physical settings. Probably, however, the dose has the strongest influence, as some substances are pleasurable and beneficial when consumed in small doses, but turn into harmful or even fatal substances in higher doses, which applies even to inconspicuous substances like the 'laughing gas'. Interestingly, this was already hypothesized nearly 500 years ago, when Paracelsus said: "sola dosis facit venenum" ("The dose makes the poison.") [4].



[1] http://bit.ly/2sQmE25
[2] http://bit.ly/2sFAVjn
[3] Leary, Universe Books, Inc., New York 1964
[4] Paracelsus, Septem Defensionenes, 1538

By Anahita Poshtiban, PhD Student AG Plested
 

This article originally appeared September 2017 in CNS Volume 10, Issue 3, Spirituality in Science