Pilot study of the 5-HT 2A R agonist psilocybin in the treatment of tobacco addiction

“The Fagerström Test for Cigarette Dependence (FTCD; formerly Fagerström Test for Nicotine Dependence) is a 6-item questionnaire widely used to characterize the level of dependence of cigarette smokers (Fagerström, 2012; Heatherton et al., 1991).”

“The TLFB is a self-report calendar completed retrospectively by participants indicating the number of cigarettes smoked each day (Sobell and Sobell, 1992).”

“Two measures of recent smoking, exhaled carbon monoxide (CO) and urinary cotinine level (Benowitz et al., 2002), were assessed at intake, weekly throughout the intervention, and at 6-month follow-up.”

“This 100- item questionnaire has previously been used to characterize the subjective effects of psilocybin (Griffiths et al., 2006, 2011).”

“For example, when paired with 12 brief weekly counseling meetings, pharmacotherapies have shown seven-day point prevalence abstinence rates of 24.9% to 26.3% (bupropion) and 33.5% to 35.2% (varenicline) at approximately 6 months post-TQD (Gonzales et al., 2006; Jorenby et al., 2006).”

“For example, when paired with 12 brief weekly counseling meetings, pharmacotherapies have shown seven-day point prevalence abstinence rates of 24.9% to 26.3% (bupropion) and 33.5% to 35.2% (varenicline) at approximately 6 months post-TQD (Gonzales et al., 2006; Jorenby et al., 2006).”

“Several plausible mechanisms of hallucinogen-facilitated treatments have been proposed (Bogenschutz and Pommy, 2012; Carhart-Harris et al., 2012, 2014; Ross, 2012; Vollenweider and Kometer, 2010).”

“Consistent with previous findings (Griffiths et al., 2006; Grob et al., 2011), blood pressure and heart rate were elevated during drug effects, with peak values occurring on average between 1.5 and 2.5 hours post-psilocybin administration.”

“For each session a physician was on call, and rescue medications were available in case of adverse cardiovascular or psychological events (Johnson et al., 2008).”

“Several plausible mechanisms of hallucinogen-facilitated treatments have been proposed (Bogenschutz and Pommy, 2012; Carhart-Harris et al., 2012, 2014; Ross, 2012; Vollenweider and Kometer, 2010).”

“Smoking lapses were defined as any discrete instances of smoking (even a puff of a cigarette) post-TQD, while relapses were defined as smoking on seven or more consecutive days after TQD (Hughes et al., 2003).”

“The Fagerström Test for Cigarette Dependence (FTCD; formerly Fagerström Test for Nicotine Dependence) is a 6-item questionnaire widely used to characterize the level of dependence of cigarette smokers (Fagerström, 2012; Heatherton et al., 1991).”

“The Questionnaire on Smoking Urges (QSU) is a multidimensional assessment of smoking craving with demonstrated sensitivity to smoking cessation (Tiffany and Drobes, 1991).”

“This 145-item questionnaire was designed to measure changes in attitudes, moods, behavior, and spiritual experience, and has demonstrated sensitivity to the intermediate and long-term effects of psilocybin (Griffiths et al., 2008, 2011).”

“Moreover, at 14-month follow-up, 61% of volunteers associated these experiences with moderate to extreme positive behavior change (Griffiths et al., 2008).”

“This 32-item questionnaire was designed to assess primary mystical experience across the lifetime (Hood, 1975), and has been employed extensively in research, demonstrating good validity, and cross-cultural reliability (Hood et al.”

“Several plausible mechanisms of hallucinogen-facilitated treatments have been proposed (Bogenschutz and Pommy, 2012; Carhart-Harris et al., 2012, 2014; Ross, 2012; Vollenweider and Kometer, 2010).”

“Although there is experimental evidence suggesting safety and efficacy of classic hallucinogens in the treatment of addiction, this is largely in relation to the use of LSD for treating alcoholism (Krebs and Johansen, 2012; Mangini, 1998).”

“The Smoking Abstinence Self-Efficacy scale (SASE) provides a measure of smokers’ confidence to abstain from smoking in 20 hypothetical situations, and temptation to smoke in those situations, and has been found to correlate with smoking cessation outcomes (DiClemente and Prochaska, 1985; DiClemente et al., 1985).”

“Urine cotinine levels of <200 ng/mL, and breath CO of ⩽6ppm were considered as biological verification of nonsmoking status (Bramer and Kallungal, 2003; Javors et al., 2005; Middleton and Morice, 2000).”

“Despite suggestive findings, this line of investigation was abandoned due to controversy surrounding the recreational use of hallucinogens and regulatory restrictions impeding subsequent research with 5-HT2AR agonists (Mangini, 1998; Nutt et al., 2013).”

“The Wisconsin Smoking Withdrawal Scale (WSWS) measures severity of smoking withdrawal and exhibits good validity and reliability in smoking cessation studies (Shiffman et al., 2004; Welsch et al., 1999).”

“The Wisconsin Smoking Withdrawal Scale (WSWS) measures severity of smoking withdrawal and exhibits good validity and reliability in smoking cessation studies (Shiffman et al., 2004; Welsch et al., 1999).”

“…was designed to assess primary mystical experience across the lifetime (Hood, 1975), and has been employed extensively in research, demonstrating good validity, and cross-cultural reliability (Hood et al., 2001), as well as sensitivity to the effects of psilocybin (Griffiths et al., 2006, 2011).”

“This approach was informed by studies of hallucinogen-facilitated substance dependence treatment in which investigators described an extended, time-limited, postsession period (sometimes referred to as an “afterglow”) associated with decreased substance use, elevated mood and energy, decreased anxiety, and increased c…”

“To probe for potential Hallucinogen Persisting Perception Disorder (Halpern and Pope, 2003), participants completed this 16-item questionnaire designed to assess occurrence, duration, and severity of visual disturbances (e.g. halos, strobe-like trails) at intake and 6-month follow-up.”

“Urine cotinine levels of <200 ng/mL, and breath CO of ⩽6ppm were considered as biological verification of nonsmoking status (Bramer and Kallungal, 2003; Javors et al., 2005; Middleton and Morice, 2000).”

“…scope of smoking-related mortality, and the modest success rates of approved smoking cessation treatments (Cahill et al., 2014; Gonzales et al., 2006; Jorenby et al., 2006; Mottillo et al., 2009), the novel approach presented here warrants further investigation with a randomized controlled trial.”

“…multiple sessions, which may work by extending the “afterglow” period through the time of greatest relapse risk, or by increasing the probability of a transformative mystical experience (Grinspoon and Bakalar, 1979; Halpern, 1996; Osmond et al., 1967; Savage and McCabe, 1973; Smart et al., 1966).”

“…suggest the feasibility of a psilocybin-facilitated intervention for addiction treatment, consistent with findings that increased levels of spirituality are associated with improved outcomes in drug dependence recovery (Cole et al., 2006; Galanter, 2006; Piderman et al., 2007; Piedmont, 2004).”

“Consistent with previous research administering psilocybin in controlled settings, these effects were readily managed (Griffiths et al., 2006, 2011; Grob et al., 2011; Johnson et al., 2008, 2012).”

“Several plausible mechanisms of hallucinogen-facilitated treatments have been proposed (Bogenschutz and Pommy, 2012; Carhart-Harris et al., 2012, 2014; Ross, 2012; Vollenweider and Kometer, 2010).”

“Urine cotinine levels of <200 ng/mL, and breath CO of ⩽6ppm were considered as biological verification of nonsmoking status (Bramer and Kallungal, 2003; Javors et al., 2005; Middleton and Morice, 2000).”

“For example, in two trials of extended smoking cessation treatments using a combination of bupropion, nicotine replacement, and CBT ranging from 5 to 12 months in duration, participants showed 45% to 59% seven-day point prevalence abstinence at approximately 6 months (Hall et al., 2009; Killen et al., 2008).”

“Although there is experimental evidence suggesting safety and efficacy of classic hallucinogens in the treatment of addiction, this is largely in relation to the use of LSD for treating alcoholism (Krebs and Johansen, 2012; Mangini, 1998).”

“…regarding tobacco addiction, combined with previous studies showing efficacy of 5-HT2AR agonists for treatment of alcoholism and opioid dependence (Chwelos et al., 1959; Hollister et al., 1969; Krebs and Johansen, 2012; Savage and McCabe, 1973), suggest higher-order psychological and/or…”

“…research area from the 1950s through 1970s involved the therapeutic use of 5-HT2AR agonist hallucinogens in the treatment of drug dependence, including alcohol and opioid dependence (Chwelos et al., 1959; Hollister et al., 1969; Ludwig et al., 1969; Savage and McCabe, 1973; Smart et al., 1966).”

“However, 5-HT2AR agonists do not engender compulsive drug seeking (National Institute on Drug Abuse, 2001, 2005), consistent with evidence that they are not reliably self-administered in animals (Fantegrossi et al., 2004; Griffiths et al., 1980; Poling and Bryceland, 1979).”

“…research area from the 1950s through 1970s involved the therapeutic use of 5-HT2AR agonist hallucinogens in the treatment of drug dependence, including alcohol and opioid dependence (Chwelos et al., 1959; Hollister et al., 1969; Ludwig et al., 1969; Savage and McCabe, 1973; Smart et al., 1966).”

“…research area from the 1950s through 1970s involved the therapeutic use of 5-HT2AR agonist hallucinogens in the treatment of drug dependence, including alcohol and opioid dependence (Chwelos et al., 1959; Hollister et al., 1969; Ludwig et al., 1969; Savage and McCabe, 1973; Smart et al., 1966).”

“Although participants were not drug dependent, these results suggest the feasibility of a psilocybin-facilitated intervention for addiction treatment, consistent with findings that increased levels of spirituality are associated with improved outcomes in drug dependence recovery (Cole et al., 2006; Galanter, 2006; Pid…”

“For example, in two trials of extended smoking cessation treatments using a combination of bupropion, nicotine replacement, and CBT ranging from 5 to 12 months in duration, participants showed 45% to 59% seven-day point prevalence abstinence at approximately 6 months (Hall et al., 2009; Killen et al., 2008).”

“…described an extended, time-limited, postsession period (sometimes referred to as an “afterglow”) associated with decreased substance use, elevated mood and energy, decreased anxiety, and increased capacity for close interpersonal relationships (e.g. Bowen et al., 1970; Pahnke et al., 1970).”

“As investigators have suggested, long-term abstinence may be enhanced by including multiple sessions, which may work by extending the “afterglow” period through the time of greatest relapse risk, or by increasing the probability of a transformative mystical experience (Grinspoon and Bakalar, 1979; Halpern, 1996; Osmon…”

“…trial of the Quit for Life CBT program that provided the primary foundation for the manualized intervention used in this study found a 17.2% abstinence rate at 6-month follow-up (Sykes and Marks, 2001), although participants in our study received substantially more contact with study staff.”

“Although participants were not drug dependent, these results suggest the feasibility of a psilocybin-facilitated intervention for addiction treatment, consistent with findings that increased levels of spirituality are associated with improved outcomes in drug dependence recovery (Cole et al., 2006; Galanter, 2006; Pid…”

“Several plausible mechanisms of hallucinogen-facilitated treatments have been proposed (Bogenschutz and Pommy, 2012; Carhart-Harris et al., 2012, 2014; Ross, 2012; Vollenweider and Kometer, 2010).”

“Study treatment also included two components of an effective group-based smoking cessation therapy (Zernig et al., 2008).”

“In four weekly preparation meetings, participants received smoking cessation CBT (Marks, 1993; Perkins et al., 2007), largely based on the Quit For Life program (Table 2), shown to be effective in controlled studies (Marks and Sykes, 2002; Sykes and Marks, 2001).”

“However, 5-HT2AR agonists do not engender compulsive drug seeking (National Institute on Drug Abuse, 2001, 2005), consistent with evidence that they are not reliably self-administered in animals (Fantegrossi et al., 2004; Griffiths et al., 1980; Poling and Bryceland, 1979).”

“Although participants were not drug dependent, these results suggest the feasibility of a psilocybin-facilitated intervention for addiction treatment, consistent with findings that increased levels of spirituality are associated with improved outcomes in drug dependence recovery (Cole et al., 2006; Galanter, 2006; Pid…”

“In a follow-up to the report by Johnson et al. (2014), Garcia-Romeu et al. (2014) reported that abstainers scored significantly higher on a measure of psilocybinoccasioned mystical experience.”

“It is further corroborated by recent open-label trials using psilocybin-assisted psychotherapy to treat tobacco addiction (Garcia-Romeu et al., 2014; Johnson et al., 2014) and alcoholism (Bogenschutz et al.”

“A recent pilot study of psilocybin as an adjunct in smoking cessation treatment resulted in remarkable rates of abstinence (80% point abstinence at 6-month follow-up) (Johnson et al., 2014).”

“Psilocybin has shown promise in the treatment of obsessive compulsive disorder (Moreno et al. 2006), alcohol (Bogenschutz et al. 2015) and tobacco addiction (Johnson et al. 2014) and anxiety related to terminal diagnoses (Griffiths et al. 2016; Ross et al. 2016; Grob et al. 2011).”