Roland R.

Griffiths is a professorin the departments of psychiatry

and neurosciences at the Johns HopkinsUniversitySchool of
Medicine.Hisprincipalresearch focus has been on the behavioral
and subjective effectsof mood-altering drugs. He is the lead
investigatorof the psilocybinresearch initiativeat Johns Hopkins.

Charles S. Grob is a professorof psychiatryand pediatricsat the

DavidGeffenSchoolof Medicine at UCLAand director of the Division
of Childand Adolescent Psychiatryat Harbor-UCLAMedical Center.
He has conducted clinicalresearch with several hallucinogenicdrugs.
includinglookingat psilocybinfor treating anxiety in cancer patients.

HEALTH

Hallucinogens
asMedicine
In a matter of hours, mind-altering substances may induce
profound psychological realignments that can take decades
to achieve on a therapist's couch

By Roland R. Griffiths and Charles S. Grob

ANDY LUNDAHL, A 50-YEAR-OLD HEALTH EDUCATOR, RE- The capsules contained a high dose of psilocybin, the princi-
ported to the behavioral biology research center at pal constituent of "magic" mushrooms, which, like LSD and
the Johns Hopkins University School of Medicine mescaline, produces changes in mood and perception yet only
one spring morning in 2004. She had volunteered very rarely actual hallucinations. At the end ofthe session, when
to become a subject in one of the first studies of hal- the psilocybin effects had dissipated, Lundahl, who had never
lucinogenic drugs in the US_ in more than three de- before taken a hallucinogen, completed more questionnaires.
cades. She completed questionnaires, chatted with Her responses indicated that during the time spent in the ses-
the two monitors who would be with her throughout the eight sion room she had gone through a profound mystical-like expe-
hours ahead, and settled herself in the comfortable, living-room- rience similar to those reported by spiritual seekers in many
like space where the session would take place. She then swallowed cultures and across the ages-one characterized by a sense of in-
two blue capsules and reclined on a couch. To help her relax and terconnectedness with all people and things, accompanied by
focus inward, she donned eyeshades and headphones, through the feeling of transcending time and space, and of sacredness
which a program of specially selected classical music played. and joy.

IN BRIEF

. Hundreds of research reports on halluci- Hints from the early set of studies sug- A new wave of studies on hallucinogens. Early results from new trials point to the
! nogens appeared during the 1950s and gesting that these chemicals might help primarily psilocybin, has begun to ad- promise of these therapies. with some
1960s. Illicit use resulted in outlawing of treat patients with various psychiatric dress whether the drugs can effectively patients reporting profound spiritual ex-
the drugs. Restrictions on research. disorders were not pursued because of treat the anxiety of cancer patients or periences and. hence, the ability to make
moreover, brought studies to a halt. strictures on research. help addicts kick their habits. important lifechanges.

Photograph by James Worrell December 2010, ScientificAmerican.com 77

 At a follow-up visit more than a year later, she said she con- havior-changes that might take years of effort to achieve with
tinued to think about the experience every day and-most re- conventional psychological therapy. The Johns Hopkins work is
markably-that she regarded it as the most personally meaning- so exciting because it demonstrates that such experiences can
ful and spiritually significant event of her life. She felt it had be elicited in a lab in most subjects studied. It permits, for the
brought on positive changes in her moods, attitudes and behav- first time, rigorous, prospective scientific investigations that
iors, as well as a noticeable increase in overall life satisfaction. track volunteers before and after taking the drug. This type of
"It seems like the experience triggered a quickening of my spiri- study enables researchers to examine the causes and psycholog-
tual unfolding or development;' she wrote. "Ripples of insight ical and behavioral effects of these extraordinary experiences.
still occur ... [I am] much more loving-making up for the past In its recent study the Johns Hopkins investigators used
hurts I've inflicted ... More and more I'm able to perceive people questionnaires originally designed to assess mystical experienc-
.as having the light of the divine flowing through them:' es that occurred on their own without drugs. They also looked
Lundahl was one of 36 participants in a study conducted by at overall psychological states at two and 14 months after the
one of us (Griffiths) at Johns Hopkins that began in 2001 and psilocybin session. The data showed that participants experi-
was published in 2006, with a follow-up report published two enced increased self-confidence, a greater sense of inner con-
years later. When the initial paper appeared in the journal Psy- tentment, a better ability to tolerate frustration, decreased ner-
chopharmacology, many in the scientific community welcomed vousness and an increase in overall well-being. Ratings of their
the revival of a research area that had long been dormant. Psilo- behavior by friends, family members and work colleagues unin-
cybin studies at Johns Hopkins continue along two tracks: One formed about the drug experience were consistent with the par-
explores the drug's psychospiritual effects in healthy volunteers. ticipants' self-ratings. One typical comment from a subject: "The
The other delves into whether hallucinogen-induced states of al- sense that all is One, that I experienced the essence of the uni-
tered consciousness-and, in particular, mystical-like experienc- verse and the knowing that God asks nothing of us except to re-
es-might ease various psychiatric and behavioral disorders, in- ceive love. I am not alone. I do not fear death. I am more patient
cluding some for which current therapies are not very effective. with myself:' Another participant was so inspired that she wrote
The main drug used in these studies is psilocybin, a so-called an entire book about her experiences.
classic hallucinogen. As with other drugs in this class-psilocin,
mescaline, DMT and LSD-psilocybin acts on brain cell recep- RELIEF OF SUFFERING
tors for the signaling molecule serotonin. Confusingly, substanc- WHEN RESEARCH INTO hallucinogen-based therapy stalled some
es from other drug classes that exert pharmacological effects dif- 40 years ago, it left a to-do list that included the treatment of al-
ferent from those of the classic hallucinogens also bear the "hal- coholism and other drug addictions, anxiety associated with
lucinogen" label in popular media and epidemiological reports. cancer, obsessive-compulsive disorder, post-traumatic stress
These compounds, some of which may also offer therapeutic po- disorder, psychosomatic disorder, severe character pathology
tential, include ketamine, MDMA (which is familiar as "ecsta- and autism. Back then, most published reports were anecdotal
sy"), salvinorin A and ibogaine, among others. accounts of treatments with hallucinogens, furnishing much
weaker evidence than that from controlled clinical trials. Even
OVERCOMING LEARY'S LEGACY the best studies of the era did not incorporate the stringent con-
THERAPEUTIC RESEARCH with hallucinogens pursues tantalizing trol conditions and methodologies that have become standard
evidence from studies begun in the 1950s that collectively in- in modern clinical psychopharmacology research.
volved thousands of participants. Some of these studies hinted With cancer, patients frequently confront severe anxiety and
that hallucinogens could help treat substance addiction and re- depression, and antidepressants and anxiety-reducing drugs
lieve the psychological distress of terminal illness. This research may be of limited help. In the 1960s and early 1970s more than
came to a halt in the early 1970s, as recreational use of the hallu- 200 cancer patients received classic hallucinogens in a series of
cinogens, mostly LSD, grew and garnered sensationalistic me- clinical studies. In 1964 Eric Kast of Chicago Medical School,
dia coverage. The field had also been tainted by the widely pub- who administered LSD to terminal patients with severe pain, re-
licized dismissal of Timothy Leary and Richard Alpert from ported that the patients developed "a peculiar disregard for the
Harvard University in 1963 in response to concerns about un- gravity of their situations and talked freely about their impend-
conventional research methods using hallucinogens, including, ing death with an affect considered inappropriate in our West-
in Alpert's case, giving psilocybin to a student off campus. ern civilization but most beneficial to their psychic states:' Sub-
The burgeoning and unsupervised use of the little-under- sequent studies by Stanislav Grof, William Richards and their
stood substances, partly a result of Leary's charismatic advocacy, colleagues at Spring Grove State Hospital near Baltimore (and
generated a backlash. The 1970 Controlled Substances Act placed later at the Maryland Psychiatric Research Center) used LSD
common hallucinogens in Schedule I, its most restrictive catego- and another classic hallucinogen DPT (dipropyltryptamine).
ry. New limitations were placed on human research, federal The trials showed decreases in depression, anxiety and fear of
funding ceased, and investigators involved in this line of re- death, and patients who had a mystical-type experience had the
search found themselves professionally marginalized. most improvements in psychological measures of well-being.
Decades passed before the anxiety-ridden attitudes that had One of us (Grob) has updated this work. In September a paper
blocked investigation subsided enough to allow rigorous human in theATchives ofGenemlPsychiatry reported on a 2004-2008 pi-
studies with these much storied substances. The mystical-like lot study at the Harbor-UCLA Medical Center to assess whether
experiences brought about by hallucinogens interest research- psilocybin sessions reduced anxiety in 12 terminal cancer patients.
ers particularly because such experiences have the potential to Although the study was too small to yield definitive conclusions, it
produce rapid and enduring positive changes in moods and be- was encouraging: the patients showed diminished anxiety and

78 Scientific American, December 2010

improved mood, even several months after the psilocybin session.
As with studies conducted years ago, participants also reported
The latest times abused (used in a manner
that jeopardizes the safety of the
less fear of impending death. Johns Hopkins and New York Uni- round of users or others), they are not typ-
versity have now undertaken studies with cancer patients using hallucinogen ically considered drugs of addic-
higher doses of psilocybin-ones more likely to induce the mysti- tion, because they neither pro-
cal-like experiences that earlier investigations indicated were piv- research is mote compulsive drug taking nor
otal to lasting therapeutic benefits. In Switzerland a similar pilot helping to induce a withdrawal syndrome.
study has begun using LSD instead of psilocybin. To help minimize adverse reac-
Alcoholics, cigarette smokers and other substance abusers
determine tions, the Johns Hopkins group
sometimes report beating their addictions after a deeply affect- whether these recently published a set of safety
ing mystical experience that occurred spontaneously without guidelines for conducting high-
drugs. The first wave of clinical hallucinogen research recog-
drugs can wean dose hallucinogen studies. Given
nized the potential therapeutic power of these transformative people from researchers' ability to manage
experiences. More than 1,300 patients participated in addiction drug risks, we feel that studies of
studies that yielded more than two dozen publications decades
addictions these substances should contin-
ago. Some of those studies administered high doses to minimally or allay the ue because of their potential abil-
prepared patients with little psychological support, a few of anxiety of ity to transform the life of, say, a
whom were even physically strapped to their beds. Researchers cancer patient or drug addict. If
who appreciated the importance of "set and setting" and who cancer patients. hallucinogens prove themselves
provided better support to patients tended to see better results. useful in the treatment of sub-
This earlier work yielded promising but inconclusive results. stance abuse or the existential anxiety associated with life-threat-
The new generation of hallucinogen research, with its better ening illness, further investigations could explore whether drug-
methodologies, should be able to determine whether these drugs induced experiences might be incorporated into therapies relat-
can in fact help people overcome their addictions. At Johns Hop- ed to major public health problems, such as eating disorders,
kins, Griffiths, Matthew Johnson and their colleagues have be- risky sexual behavior or a wider set of maladaptive behaviors.
gun a smoking cessation pilot study using psilocybin sessions to Benefits may also come from neuroimaging and pharmaco-
supplement cognitive-behavioral therapy, a form of treatment logical techniques that did not exist in the 1960s, which provide
that teaches patients how to change their thoughts and behav- a better understanding of how these drugs work. Imaging of the
iors to quit and remain abstinent. brain areas involved in the intense emotions and thoughts peo-
Beyond treating addictions, studies have recently started to ple have under the drugs' influence will provide a window into
test whether psilocybin can help allay the symptoms of obsessive- the underlying physiology of mystical-type experiences pro-
compulsive disorder. Other controlled substances with different duced by hallucinogens. Further research may also yield non-
mechanisms of action are also showing therapeutic potential. Re- pharmacological approaches that work more quickly and effec-
cent investigations demonstrated that ketamine, given in low tively than traditional spiritual practices such as meditation or
doses (it is normally used as an anesthetic), could provide more fasting to produce mystical experiences and desired behavioral
rapid relief from depression than traditional antidepressants changes-the kind of experience that convinced Bill Wilson in
such as Prozac. A recent trial in South Carolina used MDMA to Towns Hospital in New York City to stop drinking and inspired
successfully treat post-traumatic stress disorder in patients whom him to found Alcoholics Anonymous in the 1930s.
conventional therapies had failed to help. Similar MDMA trials Understanding how mystical experiences can engender be-
are under way in Switzerland and Israel. nevolent attitudes toward oneself and others will, in turn, aid in
explaining the well-documented protective role of spirituality in
RISKS AND THE ROAD AHEAD psychological well-being and health. Mystical experiences can
FOR THERAPIES using the classic hallucinogens to gain accep- bring about a profound and enduring sense of the interconnect-
tance, they will have to overcome concerns that emerged with edness of all people and things-a perspective that underlies the
the drug excesses of the "psychedelic '60s:' Hallucinogens can ethical teachings of the world's religious and spiritual traditions.
sometimes induce anxiety, paranoia or panic, which in unsu- A grasp of the biology of the classic hallucinogens, then, could
pervised settings can escalate to accidental injuries or suicide. help clarify the mechanisms underlying human ethical and co-
In the Johns Hopkins study, even after careful screening and at operative behavior-knowledge that, we believe, may ultimately
least eight hours of preparation with a clinical psychologist, be crucial to the survival of the human species. I!!
about a third of the participants experienced some period of
MORE TO EXPLORE
significant fear and about a fifth felt paranoia sometime during
the session. But in the supportive, homelike setting provided in Hallucinogens: A Reader. Edited by Olarles S. Grob. Tarcher. 2002.
Psilocybin Can Occasion Mystical-Type Experiences Having Substantial and Sustained
the research center and with the constant presence of trained
Personal Meaning and Spiritual Significance. R. R. Griffiths et al. in Psychopharmacology. Vol. 187,
guides, the Johns Hopkins participants encountered no lasting No.3; pages 268-283; August 2006. csp.orglpsilocybin
ill effects. Human Hallucinogen Research: Guidelines for Safety. M. W Johnson. W A Richards and R R.
Other potential risks of hallucinogens include prolonged psy- Griffiths inJoumal of Psyohopharmacology. Vol.22. No.6; pages 603-620; August 2008.
chosis, psychological distress, or disturbances in vision or other Pilot Study of Psilocybin Treatment for Anxiety in Patients with Advanoed-Stage Cancer.
Charles S. Grob etal. in Archives of General Psyohiatry Published online September 6. 2010.
senses lasting days or even longer. Such effects occur infrequent-
Johns Hopkins Psilocybin Cancer Project: www.cancer-insight.org
ly and even more rarely in carefully screened and psychologically
prepared volunteers. Although classic hallucinogens are some- READ ABOUT A PSILOCYBIN EXPERIENCE www5cientificAmerican.comlpsilocybin-book

December 2010, ScientificAmerican.com 79