Open-label study of consecutive ibogaine and 5-MeO-DMT assisted-therapy for trauma-exposed male Special Operations Forces Veterans: prospective data from a clinical program in Mexico

ABSTRACT

Background: Research in psychedelic medicine has focused primarily on civilian populations. Further study is needed to understand whether these treatments are effective for Veteran populations.

Objectives: Here, we examine the effectiveness of psychedelic-assisted therapy among trauma-exposed Special Operations Forces Veterans (SOFV) seeking treatment for cognitive and mental health problems in Mexico.

Methods: Data were collected from an ibogaine and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) clinical treatment program for SOFV with a history of trauma exposure. This clinical program collects prospective clinical program evaluation data, such as background characteristics, symptom severity, functioning (e.g., satisfaction with life, posttraumatic stress disorder symptoms, depression symptoms, anxiety symptoms, sleep disturbance, psychological flexibility, disability in functioning, cognitive functioning, neurobehavioral symptoms, anger, suicidal ideation), and substance persisting/enduring effects through online surveys at four timepoints (baseline/pre-treatment, one-, three-, and six-months after treatment).

Results: The majority of the sample (n = 86; Mean Age = 42.88, SD = 7.88) were Caucasian (87.2%), non-Hispanic (89.5%), and males (100%). There were significant and large improvements in self-reported PTSD symptoms (p < .001, d = .414), depression (p < .001, d = .275), anxiety (p < .001, d = .276), insomnia severity (p < .001, d = .351), and post-concussive symptoms (p < .001, d = .389) as well as self-reported satisfaction with life (p < .001, d = .371), psychological flexibility (p < .001, d = .313) and cognitive functioning (p < .001, d = .265) from baseline to one-month follow-up.

Conclusions: Data suggest combined ibogaine and 5-MeO-DMT assisted therapy has potential to provide rapid and robust changes in mental health functioning with a signal of durable therapeutic effects up to 6-months. Future research in controlled settings is warranted.

KEYWORDS:

• Psychedelic
• special operations veterans
• trauma
• ibogaine
• 5-MeO-DMT

Introduction

Special Operations Forces (SOF) personnel constitute the most elite members of the military, selected due to their outstanding physical and psychological resilience and are further trained to adapt to challenges of combat (1,2). However, as part of their duties, SOF Veterans (SOFV) are more likely to have a greater number of deployments, a longer time away from home, experience greater isolation, and be exposed to intense combat experiences, which can be traumatic and are related to a greater possibility for a constellation of symptoms related to stress- and trauma-exposure (2,3). In limited studies, SOFV with posttraumatic stress disorder (PTSD) symptoms also may be more reluctant to seek psychological therapy or mental health treatment out of a sense of duty to their units and stigma (3). Further, a signature injury of conflicts in Iraq and Afghanistan is traumatic brain injury (TBI). Veterans with TBI are more likely to have comorbid psychological and neuropsychiatric issues, including PTSD, depression, anxiety, cognitive impairment, and suicidal thoughts and behaviors (4). TBI also presents an interesting confound for treatment compliance and participation if people forget appointments, forget to take medications or perhaps double up without realizing, and/or are more easily cognitively fatigued and distracted (5). Currently, concerns for mental health crises and incidence of suicides among SOFV are alarmingly increasing in the context of limited effective treatment methods for this unique population (3,6). For instance, according to a study by Kashiwa et al. (7), approximately 22 veterans commit suicide daily. In the past few years, the number of active military and Veteran suicides has surpassed combat deaths and civilian suicide rates (8). In 2018, SOFV suicide rates tripled from years prior (9). Novel treatments are urgently needed to help improve quality of life, reduce the constellation of stress- and trauma-related symptoms, and decrease suicides in this population.

Currently, available treatments for traumatic stress demonstrate limited efficacy in addressing the complex spectrum of psychiatric symptoms among SOFV (10). Existing approved psychotherapies that are effective for addressing troubling memories, such as Cognitive Processing Therapy (CPT), Prolonged Exposure (PE), and Eye Movement Desensitization and Reprocessing (EMDR), have been shown to not work for all Veterans due to their complex and unique psychiatric symptoms (11). Further, a recent study comparing PE and CPT found very high dropout rates (12). For example, a recent study analyzing data on 796 patients attending a Veterans Affairs PTSD and anxiety clinic for CPT or PE treatment found that only 11.4% of patients initiated either CPT or PE, and only 7.9% completed either treatment (13). Moreover, data indicated that CPT dropouts primarily occur after three sessions and PE patients tend to discontinue their treatment after two sessions (14). Pharmacotherapies, such as selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, mood stabilizers, antipsychotics, or psychostimulants, which are usually prescribed to patients to reduce their persistent physiological arousal, mood symptoms, or mitigate cognitive deficits (15,16), demonstrate limited efficacy for many individuals with PTSD (17) with unwanted side effects and long-term use requirements (11,18,19). Given the comorbid psychological and neuropsychiatric issues associated with PTSD symptoms, some have argued for the need to develop transdiagnostic treatments that can simultaneously address PTSD and common overlapping comorbidities presenting in the Veteran population (20,21).

In recent years, there has been increasing interest in investigating the use of psychedelic medicines as adjuncts in the treatment of various psychiatric conditions, including depression and anxiety (22,23), obsessive-compulsive disorder (24), substance use disorders (25–28), and PTSD (29–32). For example, findings from several clinical trials have shown robust decreases in PTSD symptoms at follow-up, with approximately 80% of patients with PTSD showing a clinical response to this type of psychedelic-assisted adjunct treatment (e.g., MDMA, psilocybin) (30–32). Recent phase 3 results found that relative to manualized treatment and placebo, MDMA-assisted therapy was highly efficacious in individuals with severe PTSD, and treatment was safe and well-tolerated, even in those with comorbidities (25).

There is also emerging evidence exploring the administration of ibogaine and 5-MeO-DMT in therapeutic settings, which may be of particular relevance for addressing the complex constellation of symptoms experienced by SOFV and other Veterans (33). Ibogaine and 5-MeO-DMT are psychoactive drugs, and both classified as Schedule I controlled substances under the Controlled Substance Act (CSA) in the United States (34). Ibogaine is a plant-derived hallucinogenic alkaloid used traditionally in African spiritual practices, while 5-MeO-DMT (a close relative to DMT) is a naturally occurring compound found in certain plants and toad secretions and has been used in spiritual practices (35). Clinics that choose to integrate ibogaine and 5-MeO-DMT into the same treatment experience believe that combining medicines may potentially be more effective. Davis and colleagues recently published the results of a retrospective survey study that examined a small group of SOFV (n = 51) with trauma-related psychological and cognitive impairment, and who sought psychedelic-assisted therapy with ibogaine and 5-MeO-DMT in Mexico. Results indicated significant and very large self-reported reductions in suicidal ideation, cognitive impairment, and symptoms of PTSD, depression, and anxiety from before-to-after the psychedelic therapy (33). Results also showed a significant and large increase in psychological flexibility from before-to-after the psychedelic treatment, which was strongly associated with reductions in cognitive impairment, improvement in symptoms of PTSD, depression, and anxiety, suggesting that alterations in psychological flexibility mediate the effect of psychedelic therapy on mental health outcomes (33). Additionally, most participants rated the psychedelic experiences as one of the top five personally meaningful, spiritually significant, and psychologically insightful experiences of their entire lives (33).

Although these preliminary data are encouraging, they are cross-sectional, retrospective, and more research is needed to better understand the prospective associations of this approach among Veterans seeking this treatment. Therefore, the present study was designed to address this gap in the literature by conducting a clinical chart review study with a clinical program working with SOFV seeking ibogaine and 5-MeO-DMT in Mexico. This clinical program collects prospective clinical program evaluation data at four timepoints (baseline/pre-treatment, one-, three-, and six-months after treatment). The current study obtained these data to analyze outcomes of this program to determine whether treatment is effective in this SOFV population. Data from the proposed study will substantially advance understanding of the effectiveness of psychedelic-assisted therapies with ibogaine and 5-MeO-DMT for the treatment of cognitive and mental health problems among SOFV, with implications for all trauma-exposed populations.

Method

Clinical program

Participants for this study were English-speaking US SOFV that received treatment at atherapeutic program in Mexico that provides psychedelic-assisted therapy with ibogaine and 5-MeO-DMT. Participants were referred to the clinical program via word of mouth and were required to complete a comprehensive medical and psychological screening before enrolling to ensure safety and appropriateness for participation. Details regarding eligibility criteria are detailed in our previous report (33) and provided in the supplementary materials (see S1–1). Briefly, this evaluation included medical and psychiatric history including current and past medications, treatment history, and traumatic brain injury (TBI), a blood panel, urine drug screen, and ECG.

The clinical program took place in a residential environment in Mexico, and the retreats lasted 3 days. During the first day, a program therapist hosted a group ibogaine preparation session wherein they explained the range of effects one may experience from ibogaine, encouraged participants to identify their intentions for the experience, and advised on mindfulness techniques one might use during the session. Next, retreat attendees completed a urine toxicology screen and alcohol tests in order to verify they had not consumed any contraindicated substances, and if they passed this test, they were then administered a single oral dose (10 mg/kg) of ibogaine hydrochloride (99% purity) in a group setting with two to five other attendees. All attendees were instructed to lay on a bed in a supine position and received continuous cardiac and blood pressure monitoring and intravenous saline and electrolytes during the ibogaine session. On the second day, attendees were asked to spend most of the day integrating or reflecting on their ibogaine experience. Attendees could choose to do this introspectively or in conversation with other attendees or program staff. Support was provided by clinical program staff through one-on-one meetings and group integration sessions. On the third day, a program therapist hosted a group 5-MeO-DMT preparation session, which was similar in structure and content to the ibogaine preparation session. Then, participants were administered inhaled 5-MeO-DMT, which was administered in three incremental doses starting at 5 mg, 15 mg, and 30 mg (for a total of 50 mg) and was administered to one participant at a time. Attendees may have received a fourth (30 mg) or fifth dose (45 mg) if they had not reach observed peak effects as evidenced by an altered state of consciousness or emotional catharsis. Afterward, attendees were invited to integrate or reflect on their 5-MeO-DMT experience both individually and with the group of other attendees.

Procedure for clinical program data collection by clinic staff

From September 2019 to March 2021, clinical program evaluation surveys were sent to individuals attending the psychedelic-assisted clinical program. After enrolling in the program, attendees were sent an initial pre-retreat survey prior to their weekend-long retreat. Participants who completed the pre-retreat survey prior to attending and completed their retreat with the clinical program were also sent follow-up surveys 1-, 3-, and 6-months after the date of their treatment. Program evaluation surveys were collected through SurveyGizmo/Alchemer by a staff member who was not otherwise involved in their retreat experience. Attendees did not receive compensation.

Evaluable data for the clinical chart review study

The data that were collected from the surveys administered as part of routine clinical practice at the program and were subsequently accessed by the research team for a retrospective chart review study (approved by the Institutional Review Board at Ohio State University). Because this study is a retrospective chart review study, no consent procedures were required. Data were analyzed to evaluate whether the ibogaine- and 5-MeO-DMT-assisted therapy provided benefit across domains of mental health, cognitive functioning, and well-being in SOFV. According to the program staff, the pre-treatment survey was sent to 99 individuals who were treated in the program during the time frame for this chart review period, and 86 completed the pre-treatment and were included in this study. At the subsequent follow-ups, 71, 62, and 52 attendees completed the 1-, 3- and 6-month surveys, respectively. Of these, 44 attendees completed the program evaluation surveys at all four time points. Because completion of the program evaluation was voluntary for program attendees, some attendees missed program evaluation time points. To handle missing data, an intention-to-treat (ITT) model was used to generate a conservative estimate of the overall treatment effect (36). Specifically, all attendees who completed the pre-treatment questionnaires were included in the evaluable population, and in the event of missing data at a future time point (1-, 3-, or 6-months after the retreat), data from the most recently completed time point were carried over assuming no change.

Measures

Background characteristics, symptom severity, and functioning

Details regarding assessment measures used are detailed in our previous report (33) and provided in the supplementary materials (see S1–2). The following assessments were given at pre-treatment and at 1-, 3-, and 6-month follow-ups (further detail and psychometrics included in S1–2): Satisfaction with Life Scale (SWLS) (37); Posttraumatic Stress Disorder Checklist (PCL-5) (38); Patient Health Questionnaire-2 (PHQ-2) (39); Generalized Anxiety Disorder-2 (GAD-2) (40,41); Insomnia Severity Index (42); Acceptance and Action Questionnaire (AAQ-II) (43); Sheehan Disability Scale (44,45); Medical Outcomes Study – Cognitive Functioning (MOS-CF) subscale (46); Neurobehavioral Symptom Inventory (NSI) (47); Discrete Emotions Questionnaire – Anger Subscale (48); and the Depressive Symptom Index Suicidality Subscale (DSI-SS) (49,50); During the follow-ups, attendees were asked about enduring effects and to rate how personally meaningful, spiritually significant, psychologically challenging, and psychologically insightful their experience was (51).

Data analyses

We conducted frequency counts and descriptive analyses of demographic characteristics, military history, current mental health functioning, and history of head injuries. Next, using a series of repeated measures ANOVAs we evaluated differences in mean symptom scores of PTSD, depression, anxiety, and insomnia severity, as well as suicidal ideation, anger, satisfaction in life, disability in functioning, psychological functioning, cognitive functioning, and post-concussive symptoms at pre-treatment, 1-, 3-, and 6-months. An alpha of .05 was used to determine statistical significance, and effect sizes were estimated using the partial eta squared statistic. Additionally, each repeated measures ANOVA was followed with a series of post-hoc mean pairwise comparisons of to determine whether there were specific mean differences in functioning across time points. A Bonferroni-corrected alpha was used to determine statistical significance of post-hoc comparisons. Lastly, we conducted frequency counts and descriptive statistics of enduring effects (e.g., enduring changes in behavior, attitudes, and relationships) and interpretation of acute effects of their treatment (e.g., degree to which the psychedelic experience was spiritually significant, psychological insightful). All analyses were completed using SPSS v.27.

Results

Respondent characteristics

As Table 1 shows, the majority of the sample (n = 86) reported they were middle-aged (M = 42.88, SD = 7.88), Caucasian/White (87.2%), non-Hispanic (89.5%) males (100%). Approximately 90% of the sample reported having an education degree higher than a high school diploma or equivalent (GED). More than three-quarters (80.2%) of the sample reported having a nonmilitary full- or part-time employment status.

Table 1. Demographics (N = 86).

	M(SD) or %
Age	42.88 (7.88)
Sex
Male	100
Race
Caucasian/White	87.2
African American/Black	1.2
Native Hawaiian or Pacific Islander	2.3
Native American	3.5
Mixed Race	5.8
Hispanic/Latino
No	89.5
Yes	10.5
Education
High school Diploma or equivalent (GED)	9.3
Some college credit, no degree	26.7
Trade, Technical, Vocational training after high school	2.3
Associates degree	3.5
Bachelors Degree	31.4
Masters Degree	25.6
Advanced professional or Doctoral Degree (e.g., PhD, MD, etc.)	1.2
Marital or partnership status
Married and living with spouse	61.6
Living with partner	4.7
Divorced or separated	19.8
Never married	14
Non-Military Employment Status
Employed Full or Part time	80.2
Retired from nonmilitary employment	1.2
Unemployed	18.6

Military services & treatment history

As Supplemental Table S1 reveals, attendees reported serving in various military branches, including Navy (84.0%), Army (9.3%), Marine Corps (3.5%), and Air Force (1.2%). Most attendees (90.7%) reported serving in active duty in the US Armed Forces during September 2001 or later; and were deployed (90.7%) to support Operation Enduring Freedom or Iraqi Freedom. Attendees reported seeking assistance through the clinical program for a myriad of mental health concerns including: memory/concentration problems (84.9%), traumatic brain injury (TBI) (81.4%), depression (79.1%), anxiety (76.7%), PTSD (72.1%), sleep problems (67.4%), anger/rage (60.5%), and fatigue (57%). Moreover, many attendees reported being involved in diverse treatment approaches before this intervention, including dietary/nutritional recommendations (75.6%), nutraceutical supplements (62.8%), yoga (59.3%), acupuncture (54.7%), cannabis (52.3%), or psychotherapy (51.2%), and medications for medical or psychiatric purposes (46.5%; unfortunately, it is not clear if these are SSRIs or other medications from the data obtained).

Head injury(s)

As Supplemental Table S2 presents, over three-quarters (86%) of attendees reported sustaining head injuries during deployments, with causes including: blast (85.1%), fall (55.4%), vehicular (47.3%), fragment (2.7%), and bullet (1.4%). When reflecting on the consequences of the worst head injury sustained during deployment, 85.7% of attendees reported being dazed and confused and 73.8% reported having symptoms such as headache, dizziness, irritability, memory problems, balance problems, ringing in the ears, and sleep problems for hours or days after the injury. Most attendees reported experiencing problems currently related to a possible head injury that occurred during deployments, including memory problems (82.1%), irritability (76.2%), sleep problems (72.6%), and ringing in the ears (70.2%). When reflecting on head injuries while not deployed, over three-quarters (79.1%) reported having had injuries, and almost one-half (47.1%) lost consciousness. Some attendees (29.4%) reported experiencing posttraumatic memory loss for 7 days or more after the head injury occurred while not deployed. Of note, more than one-third (37.2%) of attendees reported a pre-military history of sport-related head injury, with 72% of the sample reporting sustaining two or more concussions. Further detail regarding pre-military head injury is included in the supplementary materials (see S1–3).

Primary outcomes: mental health symptoms, suicidal ideation, and cognitive functioning

As Table 2 reveals, there were significant and very large improvements in self-reported PTSD symptoms (p < .001, d = .414), depression (p < .001, d = .275), anxiety (p < .001, d = .276), insomnia severity (p < .001, d = .351), anger (p < .001, d = .402); and a significant and very large increase in self-reported satisfaction with life (p < .001, d = .371), from pre-treatment to one-month follow-up, and sustained clinical benefit at three-month and six-month follow-ups. There was a significant medium reduction in self-reported disability/functional impairment (p < .001, d = .083) from pre-treatment to one-month follow-up, and durable improvement at three-month and six-month follow-ups. Results in Table 2 also showed significant and very large increases in psychological flexibility (p < .001, d = .313) and cognitive functioning (p < .001, d = .265), and a significant and large reduction in post-concussive symptoms (p < .001, d = .389), from pre-treatment to one-month follow-up, and symptoms remained improved at one-month, three-month, and six-month follow-ups. There was also a significant and medium reduction in suicidal ideation (p < .01, d = .05), from pre-treatment to one-month follow-up.

Table 2. Primary outcomes (mental health symptoms, suicidal ideation, and cognitive functioning) summary variables (N = 86).

	Baseline	1-month	3-month	6-month	F	Post-hoc	Partial Eta Squared
(N = 86)	M (SD)	M (SD)	M (SD)	M (SD)
SWLS	19.15 (7.25)	25.28 (6.99)	24.99 (6.60)	25.15 (6.39)	50.23***	BL <1 m = 3 m = 6 m	.371
PCL-5	35.16 (15.36)	18.44 (16.23)	17.77 (13.98)	18.41 (15.08)	60.14***	BL >1 m = 3 m = 6 m	.414
PHQ2	2.88 (1.88)	1.34 (1.59)	1.42 (1.56)	1.50 (1.54)	32.30***	BL >1 m = 3 m = 6 m	.275
GAD2	2.79 (1.74)	1.34 (1.52)	1.43 (1.43)	1.57 (1.55)	32.46***	BL >1 m = 3 m = 6 m	.276
ISI	14.67 (5.85)	9.90 (6.32)	9.62 (6.08)	9.29 (6.49)	45.92***	BL >1 m = 3 m = 6 m	.351
SDS	6.49 (3.37)	4.35 (4.31)	4.62 (4.42)	5.09 (4.54)	7.68***	BL >1 m = 3 m = 6 m	.083
AAQ-II	24.69 (9.60)	17.28 (8.98)	17.06 (8.57)	16.95 (8.84)	38.67***	BL >1 m = 3 m = 6 m	.313
MOS-CF	57.36 (19.15)	73.84 (20.08)	70.47 (20.64)	73.14 (18.82)	30.68***	BL <1 m = 3 m = 6 m	.265
NSI	31.48 (13.95)	18.84 (14.50)	20.31 (13.15)	19.35 (13.35)	54.09***	BL >1 m = 3 m = 6 m	.389
DEQ-A	15.06 (6.56)	9.63 (5.72)	9.44 (4.92)	9.19 (4.96)	57.12***	BL >1 m = 3 m = 6 m	.402
DSI-SS	1.03 (1.68)	.60 (1.40)	.70 (1.47)	.67 (1.43)	4.45**	BL >1 m	.050

Note: *p < .05, **p < .01, ***p < .001; Partial Eta Squared (small = 0.01; medium = 0.06; large = 0.14); BL=Baseline; 1 m=one-month; 3 m=three-month; 6 m=six-month.

SWLS: Satisfaction with Life Scale; PCL-5: Posttraumatic Stress Disorder Checklist; PHQ2: Patient Health Questionnaire-2; GAD-2: Generalized Anxiety Disorder-2; ISI: Insomnia Severity Index; SDS: Sheehan Disability Scale; AAQ-II: Acceptance and Action Questionnaire; MOS-CF: Medical Outcomes Study – Cognitive Functioning; NSI: Neurobehavioral Symptom Inventory; DEQ-A: Discrete Emotions Questionnaire – Anger Subscale; DSI-SS: Depressive Symptom Index Suicidality Subscale.

Enduring effects

Most attendees reported experiencing moderate to strong positive desirable changes across a range of attitudes, behaviors, and relationships (see Table S4). Additionally, attendees reported the experiences were the single most meaningful (25.7% at one-month), spiritually significant (48.6% at one-month), difficult or challenging (17.1% at one-month), and psychologically insightful of their entire life (42.9% at one-month). More details, see supplementary document table 4 (pages 20–21).

Discussion

This is the first prospectively collected data from a clinical program to be analyzed regarding the potential clinical benefits of combined ibogaine and 5-MeO-DMT treatment for trauma-exposed SOFV. Consistent with our previously published retrospective findings, there were significant improvements reported by participants across multiple domains of stress- and trauma-related concerns including both specific symptom constellations as well as associated features such as life satisfaction, psychological flexibility, meaning and purpose, and spirituality. Importantly, these are not only robust improvements in symptoms and various factors relating to mental health and wellness, they are very rapid acting, with changes occurring after 3 days of intervention. Relative to gold standard traditionally available interventions, both talk- and pharmacotherapies that often require weeks to months to achieve an effect, the rapid-acting therapeutic benefits are highly advantageous.

Findings also suggest this treatment modality was effective at reducing post-concussive symptoms, which raises important questions and areas for future research, such as whether these improvements in symptoms are related to the shifting in overlapping mental health symptoms, whether they are related to the rapid and robust neurobiological changes, specifically changes in synaptic/functional connectivity, or whether it is a mixture of both (52–57). Mechanistic studies will be informative to better understand the neurobiological underpinnings of these medicines.

Significance

This is the first study of its kind, both to report on the combined therapeutic effects of ibogaine and 5-MeO-DMT assisted therapy and to report on the potential benefits of psychedelic assisted treatment for SOFV using data that was collected in a longitudinal and prospective manner. Because there is such an urgent need to find rapid acting and robust interventions with durable clinical benefit, this study has significant implications for future research and clinical practice. Further, because these interventions are conducted in small group settings, this also highlights the potential benefit of – and great need to study – the therapeutic benefits of not only ibogaine and 5-MeO-DMT but all psychedelic medicine and assisted therapies in group settings. Indigenous communities across the world have used these medicines in group and community-based healing practices for centuries, and these findings suggest the group format yields positive outcomes. This may be especially useful for some populations such as military Veterans who often have a strong sense of connection and comradery among fellow service members and Veterans. Group-based intervention has significant implications for a more widespread and accelerated path to clinical practice.

Another important finding of this study is the significant durability of effects. Participants engaged in a 3 day retreat and reported sustained symptom improvement at 1-, 3-, and even 6-months following completion of the treatment protocol. Data were not collected beyond 6-months to know when/if there was a heightening of symptoms. These findings are not dissimilar to those reported with other psychedelic medicines, with significant improvements noted soon after dosing/intervention (hours to days) and sustained, durable therapeutic effects for months or more after a treatment. If consistently replicated, this could have major implications for the landscape of mental health care if people are able to experience significant and sustained healing with 3 days of intensive treatment, relative to our traditionally available interventions that require 8–12 weeks of weekly therapy (e.g., gold standard talk therapies such as PE or CPT), or daily use of a pharmacotherapy such as an SSRI for months to years. The study sample comprising the SOFV population, which is perhaps unique in that it includes individuals who have been exposed to significant and chronic trauma, including both pre- and peri-military traumatic experiences as well as pre- and peri-military head injuries. These individuals have complicated histories with multiple physical and psychiatric health-related comorbidities. Many have been engaged in multiple types of traditionally available interventions, both the “over-the-counter” type as well as established gold-standard types such as talk therapy and pharmacotherapy.

Limitations

Adverse Effects: As these are very powerful medicines with potential for negative medical and psychiatric effects, it will be important to carefully evaluate and report on negative experiences of any kind to better categorize the overall safety profile of these interventions. Such data were not collected in the current study. Clinical/Behavioral Assessment: The assessments in the current report are solely based on self-report measures. Future research should implement carefully designed batteries that include both self-report and gold-standard clinician-administered measures to better capture symptom change, psychedelic experiences, and associated features such as meaning making, psychological insight and flexibility, and life satisfaction. Lack of Diversity: The sample lacks diversity. This is an issue not only in the current report but across much of the literature regarding psychedelic medicines and assisted therapies. Future studies must be intentionally designed to sample diverse populations to better understand the potential risks and benefits of ibogaine, 5-MeO-DMT, and other psychedelic medicines across strata including race, religion, and socioeconomic status. Especially as we know marginalized groups are at heighted risk for trauma-exposure and more likely to have limited resources and support, including access to mental health care, exploring appropriate interventions with benefit for these groups is of the utmost need. Increased diversity also needs to be a priority among the therapists/facilitators as this portion of the scientific evidence has also been “white-washed.” Regarding diversity, within Veteran samples it will be critical to examine the clinical potential of psychedelic medicine and assisted-therapies for other non-SOFV groups, perhaps with emphasis on female Veterans, Veterans with a history of military sexual trauma, and Veterans from pre-9/11 service eras. Intent to Treat: We do not have complete data for all participants. As noted, 44 completed the full assessment battery at baseline and all follow-up visits (with 71, 62, and 52 attendees completing the 1-, 3-, and 6-month surveys respectively). We took a very conservative approach to manage the missing data by bringing forward the last entries. Of course, having larger samples with more complete data across longitudinal time points will be valuable in capturing a more complete understanding of people’s experiences and the safety, tolerability, efficacy, and durability of symptom change. Lack of control group: There is no control group, neither active nor placebo, which leaves room for bias of interpretation. However, as this is a newer area of study and data are collected from measures collected as part of routine clinical practice, a control was not feasible. Future randomized and controlled trials will be important to better understand the potential benefits of ibogaine and 5-MeO-DMT. Lack of detail regarding SSRI use: The data available leave questions as to current and past use of SSRIs by the participants, which may have influenced their experiences with this treatment approach. Further detail about this would be especially helpful as this is often an indicator used in research trials for treatment-refractory or resistant symptoms.

Conclusion

This study replicates and extends our previous retrospective report and suggests potential for ibogaine and 5-MeO-DMT assisted therapies as treatment for stress- and trauma-related concerns including PTSD, depression, anxiety, suicidality, and even post-concussive symptoms. Further, participants also reported positive changes in quality of life, level of spirituality, and their sense of meaning and purpose in life. These are vital factors associated with the overall day-to-day satisfaction and sense of contentedness. Interventions with potential to not only improve symptoms but go beyond that and facilitate positive changes in one’s quality of life are important areas requiring future research in controlled settings.

Author contributions

All authors materially participated in the research and individually and significantly contributed to the preparation of the article. All authors have approved of the final article and provided any conflicts for inclusion in the disclosure.

Disclaimers

The views expressed herein are solely those of the authors and do not reflect an endorsement by or the official policy or position of Ohio State University, Johns Hopkins University, Baylor College of Medicine, the US Department of Veterans Affairs, or the US Government.

Acknowledgments

We also thank Martin Polanco of The Mission Within, for sharing the clinical chart data for analysis in this study.

Disclosure statement

AKD and LAA are board members at Source Research Foundation. AKD is a lead trainer at Fluence. Neither of these organizations were involved in this study.

Data availability statement

Data is accessible via reasonable request to the corresponding author.

Additional information

Funding

This study was funded by Veterans Exploring Treatment Solutions. AKD is supported by the Center for Psychedelic and Consciousness Research, funded by private philanthropic funding from Tim Ferriss, Matt Mullenweg, Craig Nerenberg, Blake Mycoskie, and the Steven and Alexandra Cohen Foundation. AKD, NS, and YX are also supported by the Center for Psychedelic Drug Research and Education, funded by anonymous private donors. LAA’s salary was partially supported by IK2CX001873 of the US Department of Veterans Affairs, Office of Research & Development, Clinical Science Research & Development Service and the American Foundation for Suicide Prevention (YIA-0-04-116). The funding sources have had no involvement in the study design, the collection, analysis, and interpretation of data, the writing of this report, or the decision to submit this article for publication.