Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases

Peter Gasser, Dominique Holstein, Yvonne Michel, Rick Doblin, Berra Yazar-Klosinski, Torsten Passie, Rudolf Brenneisen, Peter Gasser, Dominique Holstein, Yvonne Michel, Rick Doblin, Berra Yazar-Klosinski, Torsten Passie, Rudolf Brenneisen

Abstract

A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.

Trial registration: ClinicalTrials.gov NCT00920387.

Figures

FIGURE 1
FIGURE 1
Consolidated standards of reporting trials LSD/anxiety flow diagram.
FIGURE 2
FIGURE 2
Study outcomes. State and trait anxiety scores in the LSD and placebo group. Values are mean ± SEM of changes from baseline in eight subjects in the LSD group and three subjects in the placebo group. Measures were obtained before the first treatment session (baseline), 1 week after the first treatment (post 1 LSD), 1 week after the second treatment (LSD 2), and at follow-up after 2 months. At 2 months, state anxiety scores were significantly lower in the LSD group compared with the placebo group. The crossover group (n = 3) shows a positive trend of STAI state and trait score reduction. At 12-month follow-up, the state and trait values remain stable compared with the 2-month follow-up.

References

    1. Aaronson N, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Fletchner H, Fleischman SB, de Haes JC. (1993). The European Organization for Research and Treatment of Cancer QLQ-C30: A quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 85: 365– 376
    1. Abramson H. (Ed) (1967). The use of LSD in psychotherapy and alcoholism. New York: Bobbs-Merrill
    1. Bonson KR, Buckholtz JW, Murphy DL. (1996). Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans. Neuropsychopharmacology. 14: 425– 436
    1. Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, Tyacke RJ, Leech R, Malizia AL, Murphy K, Hobden P, Evans J, Feilding A, Wise RG, Nutt DJ. (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl Acad Sci U S A. 109: 2138– 2143
    1. de Araujo DB, Ribeiro S, Cecchi GA, Carvalho FM, Sanchez TA, Pinto JP, de Martinis BS, Crippa JA, Hallak JE, Santos AC. (2012). Seeing with the eyes shut: Neural basis of enhanced imagery following Ayahuasca ingestion. Hum Brain Mapp. 33: 2550– 2560
    1. First MB, Spitzer RL, Gibbon M, Williams JBW. (2002). Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. (SCID-I/P). New York: New York State Psychiatric Institute
    1. Gasser P. (1996). Die Psycholytische Therapie in der Schweiz von 1988–1993. Schweiz Arch Neurol Psychol. 147: 59– 65
    1. Gouzoulis-Mayfrank E, Schreckenberger M, Sabri O, Arning C, Thelen B, Spitzer M, Kovar KA, Hermle L, Bull U, Sass H. (1999). Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and D-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG. Neuropsychopharmacology. 20: 565– 581
    1. Griffiths RR, Richards WA, McCann U, Jesse R. (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology. 187: 268– 283; discussion 284–292
    1. Grinspoon L, Bakalar JB. (1997). Psychedelic drugs reconsidered. New York: Lindesmith Center
    1. Grob CS, Danforth AL, Chopra GS, Hagert M, McKay CR, Halberstadt AL, Greer GR. (2011). Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry. 68: 71– 78
    1. Grof S. (1975). Realms of the human unconscious: Observations from LSD research. New York: Viking Press
    1. Grof S. (1980). LSD psychotherapy. Pomona, CA: Hunter House Inc Publishers
    1. Grof S, Halifax J. (1978). The human encounter with death. New York: E P Dutton
    1. Herrmann-Lingen C, Buss U, Snaith RP. (2011). Hospital Anxiety and Depression Scale–Deutsche Version (HADS-D). Bern, Switzerland: Hans Huber
    1. Hintzen A, Passie T. (2010). The pharmacology of LSD. Oxford, England: Oxford University Press
    1. Hofmann A. (1979). How LSD originated. J Psychedelic Drugs. 11: 53– 60
    1. Howell D, Keller-Ollaman S, Olver T, Hack T, Broadfield L, Biggs K, Chung J, Esplen MJ, Gravelle D, Green E, Gerin-Lajoie C, Hamel M, Harth T, Johnston P, Swinton N, Syme A. (2010). A Pan-Canadian practice guideline: Screening, assessment and care of psychosocial distress (depression, anxiety) in adults with cancer. Toronto, Canada: Canadian Partnership Against Cancer (Cancer Journey Action Group) & the Canadian Association of Psychosocial Oncology
    1. Kast E, Collins V. (1964). Study of lysergic acid diethylamide as an analgesic agent. Anesth Analg. 43: 285– 291
    1. Kornetsky C. (1957). Relation of physiological and psychological effects of lysergic acid diethylamide. AMA Arch Neurol Psychiatry. 77: 657– 658
    1. Kurland AA. (1985). LSD in the supportive care of the terminally ill cancer patient. J Psychoactive Drugs. 17: 279– 290
    1. Leuner H. (1981). Halluzinogene. Bern, Switzerland: Hans Huber Verlag
    1. MacLean KA, Johnson MW, Griffiths RR. (2011). Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. J Psychopharmacol. 25: 1453– 1461
    1. McGlothlin W, Cohen S, McGlothlin MS. (1967). Long lasting effects of LSD on normals. Arch Gen Psychiatry. 17: 521– 532
    1. Mogar R. (1967). Psychedelic (LSD) research: A critical review of methods and results. In Bugental J. (Ed), Challenges of humanistic psychology (pp 135– 146). New York: McGraw Hill
    1. Multidisciplinary Association for Psychedelic Studies (2007). LSD-assisted psychotherapy in persons suffering from anxiety associated with life-threatening disesases. A phase II, double-blind, placebo-controlled dose-response pilot study. Clinical trial protocol. Retrieved from: Accessed December 5, 2007.
    1. Nichols DE. (2004). Hallucinogens. Pharmacol Ther. 101: 131– 181
    1. Pahnke WN, Kurland AA, Goodman LE, Richards WA. (1969). LSD-assisted psychotherapy with terminal cancer patients. Curr Psychiatr Ther. 9: 144– 152
    1. Pahnke WN, Kurland AA, Unger S, Savage C, Grof S. (1970). The experimental use of psychedelic (LSD) psychotherapy. JAMA. 212: 1856– 1863
    1. Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A. (2008). The pharmacology of lysergic acid diethylamide: A review. CNS Neurosci Ther. 14: 295– 314
    1. Riba J, Romero S, Grasa E, Mena E, Carrio I, Barbanj MJ. (2006). Increased frontal and paralimbic activation following ayahuasca, the pan-Amazonian inebriant. Psychopharmacology. 186: 93– 98
    1. Salzman C. (1969). Controlled therapy research with psychedelic drugs: a critique. In RE Hicks, PJ Fink (Eds), Psychedelic drugs (pp 23–32). New York: Grune & Stratton
    1. Savage C, Fadiman J, Mogar R, Hughes AM. (1966). The effects of psychedelic (LSD) therapy on values, personality, and behavior. Int J Neuropsychiatry. 2: 241– 254
    1. Schmitz N, Hartkamp N, Kiuse J, Franke GH, Reister G, Tress W. (2000). The Symptom Check-List-90-R (SCL-90-R): A German validation study. Qual Life Res. 9: 185– 193
    1. Schweizerische Krebsliga (2005). Schlussbericht Bestandesaufnahme psychosoziale Onkologie in der Schweiz. Bern, Switzerland: Krebsliga Schweiz
    1. Scott NW, Fayers PM, Aaronson NK, Bottomley A, de Graeff A, Groenvold M, Gundy C, Koller M, Petersen M, Sprangers MAG. (2008). EORTC QLQ-C30 Reference Values. Brussels, Belgium: EORTC Quality of Life Group.
    1. Sokoloff L, Perlin S, Kornetsky C, Kety SS. (1957). The effects of D-lysergic acid diethylamide on cerebral circulation and overall metabolism. Ann N Y Acad Sci. 66: 468– 477
    1. Spielberger CS, Gorsuch RL, Lushene RE. (1970). Manual for the State Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists Press
    1. Vollenweider FX. (1998). Advances and pathophysiological models of hallucinogenic drug actions in humans: A preamble to schizophrenia research. Pharmacopsychiatry. 31 (suppl 2): 92– 103
    1. Vollenweider FX, Leenders KL, Scharfetter C, Maguire P, Stadelmann O, Angst J. (1997). Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis. Neuropsychopharmacology. 16: 357– 372
    1. Wittchen HU, Zaudig M, Fydrich T. (1997). Strukturiertes klinisches Interview für DSM-IV. Achse I und II. Goettingen, Germany: Hogrefe
    1. Yensen R, Dryer D. (1992). Thirty years of psychedelic research: the Spring Grove experiment and its sequels. Unpublished manuscript, based on an address to the European College of Consciousness (ECBS) International Congress in Goettingen, Germany
    1. Zinberg NE. (1986). Drug, set, and setting: The basis for controlled intoxicant use. New Haven, CT: Yale University Press

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