Pain catastrophizing will be assessed with three items taken from the Pain Catastrophizing Scale that have been specifically validated for use in Ecological Momentary Assessment (EMA) studies of patients with chronic pain. Items will be administered via EMA and scores will be aggregated over 7-day EMA periods at baseline, post-session, and 1-month follow-up. Each item is on a 5-point Likert scale (ranging from 0, "Not at all", to 4, "All the time"). Higher scores on each of these items indicates increased pain catastrophizing.

A separate set of LMERs will be utilized for each primary endpoint (aggregated averages of momentary pain catastrophizing), with a primary LMER estimating the difference between Baseline and Week 1. The Time x Group interaction will be the primary focus of interest, and we aim to evaluate 1) the extent to which the primary endpoint differs between Baseline and Week 1, and 2) the extent to which that difference varies between the Psilocybin and Control groups.

Positive Affective Pain Inhibition will be assessed using quantitative sensory testing at baseline, 1-week post-drug-administration, and 1-month post-drug-administration. Positive affective pain inhibition is measured as the difference in pain ratings to noxious stimuli administered during the presentation of positive/rewarding stimuli relative to neutral or negative stimuli.

A separate set of LMERs will be utilized for each primary endpoint (index of Positive Affective Pain Inhibition), with a primary LMER estimating the difference between Baseline and Week 1. The Time x Group interaction will be the primary focus of interest, and we aim to evaluate 1) the extent to which the primary endpoint differs between Baseline and Week 1, and 2) the extent to which that difference varies between the Psilocybin and Control groups.

Discrete negative emotion items: depressed, angry, frustrated, and worried. Negative affect will be assessed by asking participants to rate the intensity of four discrete negative emotions (depressed, angry, frustrated, and worried) on a 5-point Likert scale from 1-5 ("Very slightly or not at all" to "Extremely") and averaging discrete items. Negative Affect scores will be aggregated over 7-day EMA periods at baseline, post-session, and 1-month follow-up. Lower Negative Affect scores represent lower levels of negative affect.

A separate set of LMERs will be utilized for each endpoint (aggregated averages of momentary negative affect), with a secondary LMER estimating the difference between Baseline and 1-Month. The Time x Group interaction will be the primary focus of interest, and we aim to evaluate 1) the extent to which the secondary endpoint differs between Baseline and 1-Month, and 2) the extent to which that difference varies between the Psilocybin and Control groups.

Pain catastrophizing will be assessed with three items taken from the Pain Catastrophizing Scale that have been specifically validated for use in Ecological Momentary Assessment (EMA) studies of patients with chronic pain. Items will be administered via EMA and scores will be aggregated over 7-day EMA periods at baseline, post-session, and 1-month follow-up. Each item is on a 5-point Likert scale (ranging from 0, "Not at all", to 4, "All the time"). Higher scores on each of these items indicates increased pain catastrophizing.

A separate set of LMERs will be utilized for each endpoint (aggregated averages of momentary pain catastrophizing), with a secondary LMER estimating the difference between Baseline and 1-Month. The Time x Group interaction will be the primary focus of interest, and we aim to evaluate 1) the extent to which the secondary endpoint differs between Baseline and 1-Month, and 2) the extent to which that difference varies between the Psilocybin and Control groups.

Positive Affective Pain Inhibition will be assessed using quantitative sensory testing at baseline, 1-week post-drug-administration, and 1-month post-drug-administration. Positive affective pain inhibition is measured as the difference in pain ratings to noxious stimuli administered during the presentation of positive/rewarding stimuli relative to neutral or negative stimuli.

A separate set of LMERs will be utilized for each endpoint (index of Positive Affective Pain Inhibition), with a secondary LMER estimating the difference between Baseline and 1-Month. The Time x Group interaction will be the primary focus of interest, and we aim to evaluate 1) the extent to which the secondary endpoint differs between Baseline and 1-Month, and 2) the extent to which that difference varies between the Psilocybin and Control groups.

Our secondary analytic strategy will focus on the dynamic association between affect and pain using the micro-longitudinal EMA data, in which the EMA data is organized hierarchically with Waves (Baseline, 1-week, 1-month) nested within People, Days nested within Waves, and Momentary Observations (up to four) nested within Days. For each EMA wave (Baseline, 1-week, and 1-month), we will utilize separate LMERs to evaluate the momentary (i) concurrent and (ii) lagged associations between affective variables and pain. In each LMER, person-mean centered day-level affective variables and Group (Psilocybin vs. Methylphenidate) will be included as fixed effects; day-level intercept and participant-level intercept will be included as random effects. Results from these LMERs will also allow us to evaluate the extent to which the momentary concurrent/lagged associations differ by group at each EMA wave.

The selected, discrete positive and negative affect items described in Primary Outcome 1 will be supplemented by a selection of discrete items derived from the Positive and Negative Affect Schedule- Expanded Form (PANAS-X) and measured via Ecological Momentary Assessment (EMA).

Pain impact will be assessed with the Pain average, interference with Enjoyment of life, and interference with General activity (PEG), which will be assessed with EMA over the course of three distinct 7-day periods at baseline, immediately following drug session, and leading up to 1-month follow-up to permit time-varying analyses of the associations of affective mechanisms with pain and function. The PEG is a three-item measure scored, with each item rated on a scale of 0-10. Higher scores indicate higher levels of pain intensity or higher levels of interference of interference with enjoyment/general activity, depending on the item. Overall, higher scores indicate higher levels of pain impact.

An electronic algometer with a 1cm2 hard rubber probe will be used to assess responses to noxious mechanical pressure, according to standard procedures. Pressure at the site is gradually increased at a steady rate and stopped when the subject indicates the stimulus is first perceived as painful and/or tolerance is reached.

The thermal (primary outcome for determination of painful stimuli, as in Primary Outcome 3) and pressure (secondary outcome for pain testing, described in Outcome 16) stimuli may be presented together or in succession to assess conditioned pain modulation.

Chronic Pain Exacerbation will be assessed via the Graded Chronic Pain Scale- Revised (GCPS-R). This scale probes the frequency of pain and the degree to which it interferes with daily life and work activities. Responding that the pain interferes more frequently results in a higher a grade. The GCPS-R is graded from 0 (Chronic Pain Absent) to 3 (High-Impact Chronic Pain).

Neuropathic pain features will be assessed with the painDETECT questionnaire (PDQ). The PDQ comprises 12 items. The resulting total score classifies pain into three groups: a score > 18 indicates that the presence of a predominant neuropathic pain component is likely, a score of 13 to 18 is considered uncertain, and a score < 13 indicates that a neuropathic pain component is not likely present.

CLBP-related disability will be assessed with the Oswestry Disability Index (ODI). The ODI is a self-administered questionnaire divided into ten sections/items designed to assess limitations of various activities of daily living. Patients are asked to select which statement they agree with most on each item/section of the index, and each section is scored on a 0-5 scale, 5 representing the greatest disability. Summed scores range from 0-50, with 0 representing "no disability" and 50 representing "completely disabled".

Emotion regulation will be assessed with the Difficulties in Emotion Regulation Scale (DERS). This is self-report scale that asks respondents how they relate to their emotions. Items are rated on a scale of 1 ("almost never") to 5 ("almost always"). Higher scores indicate more difficulty in emotion regulation.

The PROMIS-29 v2.0 profile assesses pain intensity using a single 0-10 numeric rating item and seven health domains (physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance) using four items per domain. Higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function).

Psychological Inflexibility in Pain. The PIPS is a 12-item questionnaire that aims at measuring psychological inflexibility with two subscales, Avoidance of Pain (Avoidance) and Cognitive Fusion with Pain (Fusion). The PIPS consists of 12 items rated on a 7-point scale from 1 (never true) to 7 (always true). Higher scores indicate greater levels of psychological inflexibility.

The 12-item CPVI is a brief inventory that can be used to determine which values are important to an individual and to assess the degree of success they are having in following their values. The valued domains included in the inventory are family, intimate relations, friends, work, health, and growth or learning. Participants will be asked to rate each item on a scale from 0 (not at all important / successful) to 5 (extremely important / successful). Two primary scores are obtained when scoring the CPVI. The first is a mean success rating, taken as the average of the 6 success ratings. The second score is a mean discrepancy rating, taken as the mean of the differences between importance and success.

Dispositional Positive Emotion Scale (DPES) consists of seven subscales (joy, contentment, pride, love, compassion, amusement and awe) that measure dispositional tendencies to feel positive emotions towards others in daily life. There are 38 items in total, each on a 7-point Likert scale ranging from "strongly disagree" (1) to "strongly agree" (7). Items are averaged, yielding a total score ranging from 1 to 7. Higher scores indicate greater levels of positive emotion.

Five Facet Mindfulness Questionnaire (FFMQ-15) measures mindfulness across five subscales and is used in clinical practice to assess the effect of mindfulness on psychological health. The five subscales are: observing, describing, acting with awareness, non-judgment, and non-reactivity. Results consist of a total average score and five subscale scores. Average scores are calculated by summing the responses and dividing by the number of items, and indicate the average level of agreement with the each subscale (1 = rarely true, 5 = always true). Higher scores are indicative of someone who is more mindful in their everyday life.

The subjective experience of the drug will also be assessed with the Awe Experience Scale. Items are scored on a 7-point Likert scale, and a higher score indicates individuals experience the emotion of awe more often.

The subjective experience of the drug will be assessed with the Mystical Experience Questionnaire. The MEQ30 is a 30-item questionnaire assessing mystical-type experiences (typically following psilocybin or other psychedelic drug sessions). Higher scores on this measure reflect higher incidence of mystical experiences.

The subjective experience of the drug will also be assessed with the Challenging Experience Questionnaire (CEQ), a 26-item measure assessing seven dimensions of psychedelic-occasioned challenging experiences: grief, fear, death, insanity, isolation, physical distress, and paranoia. Response are on 6-point scale from 0, "None/not at all" to 5 "Extreme (more than ever before in my life)", indicating the degree to which the individual experienced each of a series of subjective effects during their drug session. Each item is divided by the maximum possible score; subscale scores are obtained by totaling all transformed items under that subscale to obtain each subscale score; total score is obtained by summing all transformed items on the questionnaire. Higher scores on both subscale and total scores indicate more challenging experiences.

The subjective experience of the drug will also be assessed with the 5D-ASC, a 94-item self-report scale that assesses the participants' alterations from normal waking consciousness. Participants are asked to rate each item on a scale of "No, not more than usually" to "Yes, much more than usually," and higher scores reflect greater alterations from normal waking consciousness.

The subjective experience of the drug will also be assessed with the Psychological Insight Questionnaire (PIQ). The PIQ consists of 23 items with two subscales: (a) Avoidance and Maladaptive Patterns Insights and (b) Goals and Adaptive Patterns Insights. Responses are on a scale from 0, "No; not at all" to 5 "Extremely (more than ever before in my life)." Subscale scores and total scores are determined by computing the mean of all items under the individual subscales (PIQ subscale scores) or all items on the questionnaire (total PIQ score). Higher sub scale and total scores reflect greater psychological insight.

Primals Inventory (PI-6): A six-item scale that probes basic beliefs about the world. Items are scored on a six-point Likert scale, from 0 ('Strongly Disagree') to 5 ('Strongly Agree). Higher scores indicates greater alignment with the primal being measured.