Psychedelic Therapy: A Review On Its Efficacy,

Dangers, And Future

I. Introduction
In recent times, psychedelic therapy has gained increasing attention, becoming a promising
alternative to various forms of conventional treatment for mental disorders. This therapy involves
psychedelic substances such as psilocybin mushrooms, ketamine, or lysergic acid in controlled
environments and with the guidance of a psychotherapist.

Historically, the use of psychedelics dates back to the 1950s and 1960s, when mental health
professionals explored their potential benefits in treating disorders such as PTSD and OCD and
anxiety and depression caused by cancer. However, due to legal restrictions and concerns
about their potential for misuse, psychedelics were banned, and research into their therapeutic
potential was almost completely halted.

In recent years, there has been a resurgence of interest in psychedelic therapy, primarily
because of the increasing prevalence of mental disorders and the lack of comprehensive and
effective treatments. Consequently, associations such as MAPS, APT, and Johns Hopkins
University resumed research, reaching auspicious results.

This review aims to provide an overview of the theoretical framework, clinical efficacy,
controversies, and the future of psychedelic therapy in the treatment of mental illness.

II. Theoretical Framework

Psychedelics are psychoactive substances with uses predating written history in shamanic
rituals and other religious contexts. They act on the prefrontal cortex, affecting serotonin
receptors and producing altered states of mind, with effects like hallucinations, intensified
feelings, mixed senses –synesthesia– and a distorted perception of time.

Recent research shows promise for psychedelics to be used as a new medical treatment for
different mental conditions –depression, anxiety, PTSD, and addictions– under rigorous
supervision and psychiatric support. Many psychedelics are under current purview: LSD,
psilocybin, ayahuasca, and ketamine are some of the most promising, though psilocybin and
ketamine enjoy better funding thanks to their particular legal standing.

The benefits of having newer, potentially better treatments for mental conditions are obvious,
but psychedelics would have an advantage over traditional treatments: they don't need to be
given over time. In many psychedelics, with psilocybin at the top of the list, it’s been observed
that occasional high doses under supervision yield stark improvement for patients compared to
a low-dose, frequent treatment. This method would avoid toxicity entirely, though it comes with
its own risks.
Research still needs to be conducted through rigorous and unbiased scientific methods.
Psychedelics could be the next step in mental health treatments, but they could also pose
dangers to an uninformed population and lead to newer blocks in this line of investigation.

III. The Current State of Psychedelic Therapy

While psychedelic substances are ancient, we can track the origin of psychedelic therapy
history to Albert Hoffman’s creation of lysergic acid diethylamide (LSD) in 1938. He expected it
to bring forth a revolution in psychiatry, and for over a decade, it looked like it might, with
thousands of patients undergoing psychedelic therapy. But the mounting governmental
restrictions and the use of these substances in recreational ways by popular counter-culture
movements halted scientific research in the following decades [1].

The law reached its strictest form in 1973 with President Richard Nixon’s Controlled Substances
Act, which classified all psychedelics as Schedule I substances, making their possession –even
for research purposes– illegal. The ban stands to this day, but the newly formed interest in
psychedelic therapies has moved states to establish their own laws on them. Oregon legalized
the broad clinical use of psilocybin in 2020, causing funding in research for its therapeutic uses
to skyrocket. Other states like Washington, Oakland, and Michigan already passed more limited
laws permitting the study of psychedelics [2].

Currently, there is more research on psychedelics for therapeutic purposes than ever before,
with promising Phase 2 research pointing at psychedelic-assisted treatment producing
long-lasting effects [3]. They're still in the early days, and while there are many reports on the
safety and benefits of psychedelics for the treatment of several conditions, the majority use
small samples and are inconclusive.

IV. Psychedelic Therapy for Specific Mental Health Disorders

As mental health problems are endemic in the world’s population, the need for novel and better
treatments becomes paramount. Psychedelics act on the prefrontal cortex, a region of the brain
that regulates mood and perception, and because of these mechanisms of action, they could
help with many mental disorders.

Depression and anxiety

The link between relief from depression and psychedelics appeared for the first time in the
sixties and seventies, with the observations of improved mood in dying patients who’d been
treated with LSD [4]. In 2011, another study on cancer patients –this time using psilocybin–
showed improvement in mood and a reduction in anxiety [5].

Since then, many studies have tried to assess how psychedelics can combat depression, but
the mechanisms of action remain obscure. There is a positive link between psychedelics, such
as LCD, psilocybin, and ayahuasca, and the reduction of depression and anxiety symptoms.
Many systematic reviews of separate studies indicate this link while noting that there is still a
need for larger studies with more diverse samples [6][7]. In these studies, psychedelics were
well-tolerated, with the most common adverse effects being transient anxiety, headaches,
nausea, and mild increases in heart rate and blood pressure.

The FDA approved esketamine, a ketamine component, in 2018 as an anti-depressive for

treatment-resistant adults suffering from major depression.

PTSD

Post-Traumatic Stress Disorder is one of the mental conditions with the highest need for
medicinal treatment, as psychotherapy is the only first line of treatment for this condition, and
PTSD remains a chronic illness after it [8].

Psychedelics are being currently considered as a possible treatment or at least a support for
psychotherapy. There have been studies with positive results using different psychedelics like
LCD, ketamine, or psilocybin. A randomized, double-blind, phase two trial administered MDMA
–commonly known as ecstasy– to service personnel with chronic PTSD of 6 months or more.
The trial found that after twelve months, the personnel taking MDMA showed a significant
decrease in PTSD symptoms and a high tolerance for the treatment, with only one serious
adverse event [9].

Thanks to many promising results from varied studies, the FDA designated MDMA-assisted
therapy as a “breakthrough therapy” in 2017 for PTSD treatment.

Addiction

Treating alcohol dependence was one of the first attempted uses for LCD in 1950, and a 2012
meta-analysis from six different trials showed that a single LCD dose is associated with a
decrease in alcohol misuse [10]. Psilocybin also shows promise, with studies finding a
predictable and well-tolerated response to it and a decrease in alcohol consumption, though
larger samples are necessary to investigate the mechanisms in action [11].

Researchers are currently studying psilocybin to treat other sorts of addiction, including tobacco
and opioids. A study showed a correlation between smoking cessation outcomes and
psilocybin-induced spiritual epiphanies during therapy [12].

Another psychedelic under study to help with substance problems is the amazonian plant
ayahuasca. The preliminary studies point toward clear anti-addictive qualities, but the
mechanism of action isn’t known [13]. Some researchers point out that this plant is taken in a
religious context, and that the beliefs and sentiment of belonging in a community may play an
important role in leaving addictions behind [14].

End-of-life anxiety

Current literature points toward the same results that investigations from the 50s did,
psychedelic-supported therapy can decrease anxiety in terminal patients without serious
adverse effects [15]. This could provide critical support, as evidence shows that nearly 20% of
patients with a cancer diagnosis develop anxiety symptoms, and over 10% fall into depression
[16].
Stress has a negative effect on the immune system, making its management a needed support
for cancer and immunocompromised patients [17].

V. Clinical Efficacy and Safety of Psychedelic Therapy

The effectiveness of psychedelic therapy remains to be proven conclusively, but there are many
promising results with many of them. Psilocybin supports therapy meant to confront traumatic
memories, decrease emotional avoidance, and depression, and increase acceptance and
self-forgiveness, all factors relevant to PTSD recovery [18]. LCD shows promising results in
depression and anxiety treatment [19].

Yet, the understanding of how these substances act is poorly understood. There are arguments
that the “otherworldly” hallucinations patients go through in the dosing sessions are required to
loosen maladaptive beliefs and support the effect of the psychedelic [20]. Others claim that
these experiences are simply indications of good receptor activation, and argue that we should
attempt to engineer non-hallucinatory psychedelics [21]. They move on to point out that the
long-lasting experiences of current psychedelics lead to poor time management in clinics and a
reduced healthcare workforce.

Such time-consuming practices are necessary, as the patient going through a psychedelic
session could go through sharp increases in anxiety, fear, and blood pressure [22]. Thankfully,
the risks are limited to the sessions, since no new clinical research showed evidence of
long-term damage.

VI. Controversies Surrounding Psychedelic Therapy

It’s no secret that the thousand of studies on psychedelics after Hoffman’s discovery stopped
because of political reasons, with the anti-establishment, anti-war youth’s recreational use of
psychedelics and Reagan’s following Controlled Substance Act. The following propaganda and
misrepresentation of psychedelics created such a negative image that only now is starting to
fade.

And since psychedelic-assisted therapy may shift the next paradigm of psychiatry, there’s a
surging need to consider the ethics of these treatments. One current problem is that the
mainstream interest in psychedelic treatments has caused many people to want to go through
these treatments. The clinical trials for psychedelics have no shortage of volunteers, and there’s
a rising illegal market exploiting this demand. Therapists have a duty to reduce risks in their
patients, so a harm-reduction approach is ideal. Serving as guides is illegal in many countries,
but providing psychotherapy before and after the act is not.

And paving the way forward is necessary, as incorporating psychedelic therapy into mainstream
medicine will be challenging. Psychologists are a vital part of mental health treatments, and their
understanding and acceptance of psychedelic therapy will be key to reducing their stigma. A
study showed tentative positive beliefs in these therapies by many psychologists, as well as a
concerning lack of knowledge [23]. Educating our own professionals is the first step to educate
society.
VII. Future Directions for Psychedelic Therapy
The potential of psychedelic therapy in the future of mental health care is vast, or in the words of
Dr. Stanislav Grof: “Psychedelics are to the study of the mind what the microscope is to biology
and the telescope is to astronomy.” They not only can offer alternative treatments for endemic
conditions such as anxiety or depression but needed release for terminal patients and
completely novel treatments for difficult conditions such as PTSD.

And because of this potential, there’s a pressing need for additional research and clinical trials.
The mechanisms of action of the different psychedelic substances are largely unknown, which
means their potential is untapped. And while these substances have the potential for abuse,
their risk is lower than some legal substances like alcohol, and keeping them as Schedule I
drugs only delays the development of life-saving treatments.

As to the integration of psychedelic therapy into mainstream medicine, it’s important to start with
the mental health professionals still clinging to outdated views on substances and addictions
[24]. The education of psychologists and other mental health professionals will lead to the
destigmatization of psychedelic therapies. The Psychedelic Harm Reduction and Integration
(PHRI) clinical approach will be key, with its harm reduction and psychedelic-assisted
psychotherapy [25].

VIII. Conclusion
Psychedelic therapy is returning to the fore of innovations in mental health medications it
enjoyed halfway through the previous century, before politics and social stigma stopped or made
it incredibly difficult to research it. Psychedelic substances such as LCD, psilocybin, MDMA,
ketamine, and ayahuasca have got promising preliminary findings in several applications. They
could support or treat issues like depression, anxiety, PTSD, and mental support for terminal
patients.

But further research is needed before any of that can happen, since basic knowledge such as
mechanisms of action are still unknown, and the Schedule I classification makes it difficult to
research. As public interest rises, harm reduction approaches like PHRI need to be
implemented while research continues.

If these treatments live up to their potential, we could see a working solution against the
depression and anxiety endemic, as well as the first medication for PTSD. It would also
implicate a decrease in government spending in the failed war on drugs and proper medical
care for people recreationally taking these substances.

IX. References
1. Grinspoon L, Bakalar JB (1979) Psychedelic Drugs Reconsidered. Basic Books: New
York.
2. Smith WR, Appelbaum PS. Two Models of Legalization of Psychedelic Substances:
Reasons for Concern. JAMA. 2021 Aug 24;326(8):697-698. PMID: 34338743; PMCID:
PMC8753745.

3. Alicia L. Danforth (2019) Embracing Neurodiversity in Psychedelic Science: A

Mixed-Methods Inquiry into the MDMA Experiences of Autistic Adults, Journal of
Psychoactive Drugs, 51:2, 146-154.

4. Pahnke WN, Kurland AA, Goodman LE, Richards WA. LSD-assisted psychotherapy with
terminal cancer patients. Curr Psychiatr Ther. 1969;9:144-52. PMID: 5348915.

5. Grob CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halberstadt AL, Greer GR.
Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer.
Arch Gen Psychiatry. 2011 Jan;68(1):71-8. Epub 2010 Sep 6. PMID: 20819978.

6. Ko K, Kopra EI, Cleare AJ, Rucker JJ. Psychedelic therapy for depressive symptoms: A
systematic review and meta-analysis. J Affect Disord. 2023 Feb 1;322:194-204. Epub
2022 Oct 7. PMID: 36209780.

7. Muttoni S, Ardissino M, John C. Classical psychedelics for the treatment of depression

and anxiety: A systematic review. J Affect Disord. 2019 Nov 1;258:11-24. Epub 2019 Jul
30. PMID: 31382100.

8. Krediet E, Bostoen T, Breeksema J, van Schagen A, Passie T, Vermetten E. Reviewing

the Potential of Psychedelics for the Treatment of PTSD. Int J Neuropsychopharmacol.
2020 Jun 24;23(6):385-400. PMID: 32170326; PMCID: PMC7311646.

9. Mithoefer MC, Mithoefer AT, Feduccia AA, Jerome L, Wagner M, Wymer J, Holland J,
Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R.
3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for
post-traumatic stress disorder in military veterans, firefighters, and police officers: a
randomised, double-blind, dose-response, phase 2 clinical trial. Lancet Psychiatry. 2018
Jun;5(6):486-497. Epub 2018 May 1. PMID: 29728331.

10. Krebs TS, Johansen PØ. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis
of randomized controlled trials. J Psychopharmacol. 2012 Jul;26(7):994-1002. Epub
2012 Mar 8. PMID: 22406913.

11. Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PC, Strassman RJ.
Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J
Psychopharmacol. 2015 Mar;29(3):289-99. Epub 2015 Jan 13. PMID: 25586396.

12. Garcia-Romeu A, Griffiths RR, Johnson MW. Psilocybin-occasioned mystical

experiences in the treatment of tobacco addiction. Curr Drug Abuse Rev.
2014;7(3):157-64. PMID: 25563443; PMCID: PMC4342293.

13. Nunes AA, Dos Santos RG, Osório FL, Sanches RF, Crippa JA, Hallak JE. Effects of
Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of
 Quantitative Studies in Animals and Humans. J Psychoactive Drugs. 2016
Jul-Aug;48(3):195-205. Epub 2016 May 26. PMID: 27230395.

14. Talin P, Sanabria E. Ayahuasca's entwined efficacy: An ethnographic study of ritual

healing from 'addiction'. Int J Drug Policy. 2017 Jun;44:23-30. Epub 2017 Apr 19. PMID:
28432902; PMCID: PMC5773453.

15. Yu CL, Yang FC, Yang SN, Tseng PT, Stubbs B, Yeh TC, Hsu CW, Li DJ, Liang CS.
Psilocybin for End-of-Life Anxiety Symptoms: A Systematic Review and Meta-Analysis.
Psychiatry Investig. 2021 Oct;18(10):958-967. Epub 2021 Oct 8. PMID: 34619818;
PMCID: PMC8542741.

16. Linden W, Vodermaier A, Mackenzie R, Greig D. Anxiety and depression after cancer
diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord. 2012 Dec
10;141(2-3):343-51. Epub 2012 Jun 21. PMID: 22727334.

17. Antoni MH, Dhabhar FS. The impact of psychosocial stress and stress management on
immune responses in patients with cancer. Cancer. 2019 May 1;125(9):1417-1431. Epub
2019 Feb 15. PMID: 30768779; PMCID: PMC6467795.

18. Khan AJ, Bradley E, O'Donovan A, Woolley J. Psilocybin for Trauma-Related Disorders.
Curr Top Behav Neurosci. 2022;56:319-332. PMID: 35711024.

19. Denson R, Sydiaha D. A controlled study of LSD treatment in alcoholism and neurosis.
Br J Psychiatry. 1970 Apr;116(533):443-5. PMID: 4392561.

20. Carhart-Harris RL, Friston KJ. REBUS and the Anarchic Brain: Toward a Unified Model
of the Brain Action of Psychedelics. Pharmacol Rev. 2019 Jul;71(3):316-344. PMID:
31221820; PMCID: PMC6588209.

21. Olson DE. The Subjective Effects of Psychedelics May Not Be Necessary for Their
Enduring Therapeutic Effects. ACS Pharmacol Transl Sci. 2020 Dec 10;4(2):563-567.
PMID: 33861218; PMCID: PMC8033607.

22. Johnson M, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety.
J Psychopharmacol. 2008 Aug;22(6):603-20. Epub 2008 Jul 1. PMID: 18593734;
PMCID: PMC3056407.

23. Alan K. Davis, Gabrielle Agin-Liebes, Megan España, Brian Pilecki & Jason Luoma
(2022) Attitudes and Beliefs about the Therapeutic Use of Psychedelic Drugs among
Psychologists in the United States, Journal of Psychoactive Drugs, 54:4, 309-318.

24. Pickard H. Responsibility without Blame for Addiction. Neuroethics. 2017;10(1):169-180.

Epub 2017 Jan 7. PMID: 28725286; PMCID: PMC5486507.

25. Gorman I, Nielson EM, Molinar A, Cassidy K, Sabbagh J. Psychedelic Harm Reduction
and Integration: A Transtheoretical Model for Clinical Practice. Front Psychol. 2021 Mar
15;12:645246. PMID: 33796055; PMCID: PMC8008322.