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).”

“An abbreviated list of that research includes a study of psilocybin administration to normal subjects at Johns Hopkins University (JHU) [78], studies of psilocybin-assisted psychotherapy in cancer patients at JHU [67] and at New York University [79], psilocybin-assisted therapy for the treatment of alcohol use disorde…”

“In the 1950s and 1960s, psychedelic drugs such as lysergic acid diethylamide (LSD) were used in psychotherapy, and modern clinical trials are re-examining their therapeutic potential (Bogenschutz et al., 2015; Gasser et al., 2014; Grob et al., 2011; Johnson et al., 2014).”

“(29, 30) was included assessing the efficacy of psilocybin-assisted therapy in n = 15 patients who met the following criteria: smoking ≥10 cigarettes per day, being healthy as determined by medical interview, multiple unsuccessful past quit attempts, and the desire to quit smoking.”

“psychedelics) may be an effective aid in the treatment of addiction (Bogenschutz et al., 2015; Garcia-Romeu et al., 2016; Johnson et al., 2014; Ross, 2012; Sessa and Johnson, 2015).”

“Recent small studies have supported the hypothesis that mystical experience is a mediator of change (Johnson et al., 2014; Bogenschutz et al., 2015), although more general measures of intensity also predicted improvement in our completed pilot AUD trial (Bogenschutz et al.”

“These studies also corroborate the results from recent clinical trials describing antidepressive, anxiolytic, and antiaddictive effects of psilocybin (Bogenschutz et al., 2015; Grob et al., 2011; Johnson et al., 2014; Moreno et al., 2006) and LSD (Gasser et al., 2014).”

“, 2015), tobacco (Johnson et al., 2014) and cocaine dependence (ClinicalTrials.”

“…treatments in this therapy could allow a direct experience with altered cognitive and emotional states which could then be leveraged in ongoing counselling to ultimately challenge and replace maladaptive thoughts and behavioral patterns (Garcia-Romeu and Richards, 2018; Johnson et al., 2014).”

“Other modern addiction treatment protocols such as psilocybin-assisted smoking cessation have used a cognitive behavioral therapy (CBT) model (Johnson et al., 2014).”

“…populations is relevant because strong associations between psychedelic peak experiences and therapeutic effects have been reported for other tryptamines (Garcia- Romeu et al., 2014; Johnson et al., 2014; Bogenschutz et al., 2015; Griffiths et al., 2016; Roseman et al., 2018; Ross et al., 2016).”

“These variables can be categorised into 3 major domains: namely, (1) factors pertaining to the individual’s psychological vulnerability (including their young age), (2) (negative) set, setting and/or matrix factors, and (3) factors linked to the substance itself—and most commonly, its (excessively high) dose and parti…”

“For other indications for which psilocybin is currently being studied (cancer-related anxiety/depression and addictions; Bogenschutz et al., 2015; Grob et al., 2011; Johnson et al., 2014), the present results also address a safety concern.”

“Psilocybin was generally well tolerated, with no serious TEAEs reported, consistent with findings of previous, smaller studies evaluating the feasibility of psilocybin administration with psychological support in patients with psychiatric disorders (Bogenschutz et al., 2015; Carhart-Harris et al., 2016, 2018; Davis et…”

“Obsessive Compulsive Disorder (46) Cluster Headaches/Migraines (47, 48) Demoralization with AIDS Diagnosis (50) Alcohol Use Disorder/Dependence (42–44) Tobacco Addiction (45) Cancer-related depression (8–10) Cancer-related anxiety (8–10) Treatment-resistant depression (7, 38, 39)”

“(57) Nicotine addiction (minimum 10 cigarettes a day multiple unsuccessful past quit attempts, and still desire to quit smoking) Open-label single arm proof of concept 2-3× administrations of psilocybin (20 mg/70 kg – moderate & 30 mg/70 kg – high).”

“Recent open-label pilot studies have found psilocybin to be a potentially effective aid for treatment of depression (Carhart-Harris et al., 2016, 2017, 2018; Davis et al., 2020), alcohol dependence (Bogenschutz et al., 2015), and tobacco dependence (Johnson et al., 2014, 2017).”

“[34]) Tobacco dependence n = 15 Weeks 2–15, 6-month follow-up 80% abstinence at 6-month follow-up Session 1: 5 weeks after PST 0.”

“The recently published pilot studies of psilocybin for alcohol and nicotine dependence have reported decreases in craving and increases in self-efficacy following psilocybin administration (Bogenschutz et al., 2015; M. W. Johnson et al., 2014).”

“tobacco [Garcia-Romeu et al., 2014; Johnson et al., 2014] and alcohol [Bogenschutz et al.”

“psychotherapy in 2006 for OCD [208], promising results have been published for applications in end of life anxiety [148,187,209], smoking cessation [210], treatment-resistant depression [211], as well as to initiate meditation/spiritual”

“…2011), and therapeutic outcomes in patients with alcohol use disorder (Bogenschutz et al., 2015), nicotine use disorder (Garcia-Romeu et al., 2015; Johnson et al., 2014, 2017), major depression (Carhart-Harris et al., 2016, 2018; Davis et al., 2020; Roseman et al., 2018) and cancer-related…”

“At follow-up surveys roughly 2 weeks and 2 months after the reference experience, between a quarter and a third of respondents considered the experience among the 10 most meaningful or spiritually significant of their lives, exhibiting lower rates of personal meaning and spiritual significance than both healthy (23, 5…”

“Psilocybin and other psychedelic compounds have attracted attention from researchers and clinicians for their potential to catalyze therapeutic change, when taken within a therapeutic setting, in people diagnosed with depression (1), obsessivecompulsive disorder (2), alcohol dependence (3), nicotine dependence (4), an…”

“Several PAP clinical trials have found that participants often report profound experiences of an existential or spiritual nature (Johnson et al., 2014; Bogenschutz et al., 2015; Belser et al., 2017; Podrebarac et al., 2021) that may hold enduring significance for them (Griffiths et al., 2006).”

“Alternatively, as highlighted above, Cognitive Behavioural Therapy (see also Wolff et al., 2020) and Motivational Enhancement Therapy (including Motivational Interviewing) could be used as therapeutic containers, as each of these has been supported by robust research as effective in supporting multiple varieties of he…”

“…2016; Os orio et al., 2015; Ross et al., 2016; Sanches et al., 2016), physiological outcomes, including breath carbon monoxide and urine cotinine (Johnson et al., 2014), and, in one case, modulation of potential neurobiological correlates of mood disorders (Carhart-Harris et al., 2017; Roseman,…”

“…in therapeutic settings, negative psychological effects are rare due to the tightly controlled inclusion criteria and extensive interpersonal support for subjects (Bogenschutz et al., 2015; Gasser et al., 2015; Grob et al., 2011; Johnson et al., 2014; Mithoefer et al., 2011; Oehen et al., 2013).”

“, 2016) and substance use disorders (Bogenschutz et al., 2015, 2018; Johnson et al., 2014; Noorani et al., 2018).”

“…there has been a resurgence of interest in the clinical study of psychedelics, and remarkable efficacy has been demonstrated in clinical trials for various psychiatric conditions such as anxiety (Gasser et al., 2014; Grob et al., 2011) and addiction (Bogenschutz et al., 2015; Johnson et al., 2014).”

“Such interest revived after a three-decade hiatus due to restrictive regulations, leading to a plethora of clinical studies testing psychedelics’ therapeutic values in diseases including obsessive compulsive disorder [27], anxiety [28, 29], depression [30–32], and substance abuse [33, 34], with encouraging efficacy ou…”

“…positive effects have been observed in clinical studies showing a decrease in depressive and anxiety symptoms (Carhart-Harris, et al., 2016; Griffiths et al., 2016; Grob et al., 2011; Ross et al., 2016) and abstinence from addictive substances (Bogenschutz et al., 2015; Johnson et al., 2014).”

“…for, for example, major depression (Carhart-Harris et al., 2016, 2018), obsessive compulsive disorder (Moreno et al., 2006), anxiety and depression associated with life-threatening cancer (Griffiths et al., 2016; Ross et al., 2016) and addiction (Bogenschutz et al., 2015; Johnson et al., 2014).”

“…et al., 2016; Grob et al., 2011; Ross et al., 2016), OCD (Moreno et al., 2006), alcohol dependence (Bogenschutz et al., 2015), tobacco addiction (Johnson et al., 2014), major depression (Carhart-Harris et al., CONTACT Catherine I. V. Bird Catherine.bird@kcl.ac.uk The Institute of Psychiatry,…”

“The MEQ has been used in numerous experimental and therapeutic trials with psilocybin (Garcia-Romeu et al., 2015; Griffiths et al., 2006, 2008, 2011; Johnson et al., 2014; MacLean et al., 2011) and in healthy volunteers with LSD and MDMA (Liechti et al., 2017).”

“, 2020), alcohol and tobacco dependence (Bogenschutz et al., 2015; Johnson et al., 2014), and cancerrelated existential distress (Griffiths et al.”

“The concomitant psycho-therapeutic models for psychedelicassisted therapy have historically been informed by humanistic and psycho-analytic approaches, however, there has been growing interest in incorporating other evidence-based therapies into the psychedelic assisted model, such as Cognitive Behavioural Therapy [CB…”

“…(Carhart-Harris et al., 2016, 2018, 2021; Davis et al., 2021a,b; Gukasyan et al., 2022), substance use disorders (Bogenschutz and Johnson, 2016; Johnson et al., 2014) and depression and anxiety secondary to a serious medical illness like cancer (Griffiths et al., 2016; Grob et al., 2011; Ross…”

“In some cases, patients receiving psychedelics also benefit from a psychotherapeutic intervention, such as cognitive behavioral therapy (CBT) (Johnson et al., 2014) or motivational enhancement therapy (Bogenschutz et al., 2015).”

“…in well-designed randomized controlled trials, may provide an interesting parsimonious treatment option for those with comorbid ADHD and SUDs, as there is promising evidence to suggest that psychedelics may be effective in treating various SUDs (Bogenschutz et al., 2015; Johnson et al., 2014).”

“Facilitating the reconnection with their social environment via increased emotional empathy may therefore contribute to clinical efficacy of hallucinogens shown in preliminary studies with addicted patients (24, 26).”

“, 2018); and can be effective in the treatment of depression, anxiety and addiction (Aday et al., 2020; Carhart-Harris et al., 2016, 2018; Davis et al., 2020; Goldberg et al., 2020; Johnson et al., 2014; Krebs and Johansen, 2012; Luoma et al., 2020).”

“For classical psychedelics, controlled human studies have enrolled patients with depression [3, 4, 6, 8, 83], alcohol use disorder [84, 85] or tobacco use disorder [86] — all of which are associated with cortical atrophy and dysfunction [17].”

“Mystical experiences are associated with therapeutic outcomes after psychedelic experiences, and much is made of this [4, 8, 9, 71, 72].”

“A pilot study of psilocybin and cognitive-behavioral therapy in people with tobacco addiction reported that 12 of 15 participants (80%) showed 7-day point prevalence abstinence at 6-month follow-up (9).”

“This recent work has foregone the use of LSD in favor of psilocybin, and has extended our knowledge of the beneficial effects of CH to nicotine dependence (Bogenschutz et al., 2015; Johnson et al., 2014).”

“…of these therapies in treating depression (Carhart-Harris et al. 2021; Davis et al. 2020), substance use disorders (Bogenschutz et al. 2015; Johnson et al. 2014), PTSD (Mitchell et al. 2021), and anxiety for patients facing terminal cancer (Griffiths et al. 2016; Grob et al. 2011; Ross et…”

“, [154, 155]) to few (at least 1, often more) preparation and integration sessions between the patients and their respective monitors/therapists present during the dosing session (e.”

“The persisting effects questionnaire (PEQ) assesses desirable and undesirable enduring effects of a hallucinogenic experience (Griffiths et al., 2006, 2011; Johnson et al., 2014).”

“…et al., 2017; Davis et al., 2019; Murphy et al., 2022; Roseman et al., 2018; van Oorsouw et al., 2022), addiction (Bogenschutz et al., 2015; Johnson et al., 2014, 2017; O’Reilly and Funk, 1964) and existential anxiety (Griffiths et al., 2016; Kurland et al., 1972; Pahnke et al., 1969;…”

“, 2002, 2007), and pilot trials of psilocybin-assisted treatment suggest efficacy for both alcohol and tobacco dependence (Bogenschutz et al., 2016; Johnson et al., 2014).”

“…(Agin-Liebes et al., 2020; Barrett et al., 2020; Carhart-Harris et al., 2016a, 2018a; Gasser et al., 2014; Griffiths et al., 2016; Grob et al., 2011; Ross et al., 2016), addiction (Bogenschutz et al., 2015; Bogenschutz and Johnson, 2016; Johnson et al., 2014, 2016) and PTSD (Krediet et al., 2020).”

“As mentioned in the Introduction, there is an increasing interest in psychedelics and 5-HT2AR agonists as putative therapeutics, not only when it comes to numerous psychiatric disorders but also for the treatment of addiction and alcoholism, cluster head aches, and various inflammatory disorders (Sewell et al., 2006;…”