This case study (n=1) reports that an 80-day course of low-dose ibogaine hydrochloride in a woman with Parkinson's disease was followed by improvements in motor symptoms, quality of life, fatigue and depression, but worse sleep. No adverse events were recorded.
Background and Aims
Parkinson's disease (PD) significantly impairs quality of life, and current treatments do not halt dopaminergic neurodegeneration. Evidence suggests that ibogaine, a naturally occurring indole alkaloid, may stimulate glial cell line-derived neurotrophic factor (GDNF) expression and affect dopamine transporter (DAT) function. This case study reports the effects of low-dose ibogaine hydrochloride on PD symptoms.
Methods
A 52-year-old female PD patient, decreasingly responsive to conventional therapy, underwent an 80-day treatment with gradually titrated daily doses of ibogaine hydrochloride (max 75 mg/day). Standardized assessments were conducted pre- and post-treatment using validated PD-specific clinical instruments; Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire-39 (PDQ-39), Parkinson's Disease Sleep Scale (PDSS-2), Parkinson's Disease Fatigue Scale-16 (PFS-16) and the Beck Depression Inventory-II (BDI-II), alongside a qualitative interview.
Results
Substantial improvements were observed in four of five assessment domains: motor symptoms (UPDRS), quality of life (PDQ-39), fatigue (PFS-16), and depression (BDI-II). Sleep quality (PDSS-2) declined, potentially due to ibogaine's stimulant properties. The patient reported reduced freezing of gait episodes, enhanced mobility, energy and mood, as well as an overall increased optimism. No adverse events were recorded.
Conclusion
This is the first known case study to use validated instruments to document symptomatic improvements in a PD patient following low-dose ibogaine treatment. While preliminary, these findings support the hypothesis that ibogaine may alleviate PD symptoms through neurotrophic, pharmacochaperone, and DAT-modulating mechanisms. Larger controlled trials are needed to evaluate its efficacy and clarify its mechanisms of action in PD.
Papers cited by this study that are also in Blossom
Alper, K. · The Alkaloids Chemistry and Biology (2001)
Brown, T. K., Alper, K. · The American Journal of Drug and Alcohol Abuse (2017)
Cameron, L. P., Tombari, R. J., Lu, J. et al. · Nature (2020)
Cherian, K. N., Keynan, J. N., Anker, L. et al. · Nature Medicine (2024)
Parkinson's disease is described as a common neurodegenerative disorder that substantially reduces quality of life through motor impairment, depression, disability, postural instability and cognitive problems. The authors note that current dopaminergic treatments help symptoms but do not stop the underlying loss of dopaminergic neurons, and that attempts to develop disease-modifying therapies have so far been unsuccessful. They frame glial cell line-derived neurotrophic factor (GDNF) as one potential avenue, but point out that earlier human studies of direct GDNF administration did not show clear benefit and were associated with substantial adverse events. Against this background, the paper highlights prior evidence that ibogaine may increase GDNF expression and influence dopamine transporter function, suggesting a possible therapeutic role in Parkinson's disease.
This paper is a single-patient case report. The researchers describe a 52-year-old woman diagnosed with Parkinson's disease in 2006, who had progressively reduced responsiveness to conventional treatment and no reported comorbidities or substance use disorder. Before treatment she was taking safinamide, ropinirole and levodopa/carbidopa/entacapone; safinamide was paused for the first 12 days because, as an MAO-B inhibitor, it might potentiate ibogaine, then later resumed by mutual decision as treatment progressed. The patient received an 80-day course of oral ibogaine hydrochloride, taken each morning before food. The initial dose was 25 mg/day, chosen cautiously to assess sensitivity and reduce potential side effects, and the dose was reviewed weekly and gradually titrated. The maximum daily dose reached 75 mg, but no single dose exceeded 50 mg at once. The text says the product contained 98.6% ibogaine HCl and was obtained commercially with a certificate of purity. Outcomes were measured before and after treatment using validated Parkinson's disease instruments: the Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire-39 (PDQ-39), Parkinson's Disease Sleep Scale-2 (PDSS-2), Parkinson's Disease Fatigue Scale-16 (PFS-16) and Beck Depression Inventory-II (BDI-II). A qualitative interview was also conducted. The extracted methods text does not clearly report any formal statistical analysis, which is consistent with the study being a descriptive case report rather than a comparative trial.
After 80 days of low-dose ibogaine hydrochloride, the patient showed reductions in symptom scores on four of the five assessed domains. The UPDRS, PDQ-39, PFS-16 and BDI-II all improved from baseline to the end of treatment, indicating better motor symptoms, quality of life, fatigue and depressive symptoms. The one domain that worsened was sleep: PDSS-2 scores indicated poorer sleep quality by the end of the treatment period. Qualitatively, the patient reported that improvements became noticeable after about two weeks and were increasingly apparent by four weeks. She described better energy, flexibility and movement efficiency, as well as a brighter mood and greater optimism. The results text also states that she reported fewer freezing-of-gait episodes and an overall sense of improved wellbeing. No adverse events were recorded during the treatment period.
The authors interpret this case as the first report to use validated instruments to examine ibogaine for Parkinson's disease symptoms. They argue that the pattern of change suggests ibogaine may help relieve several Parkinson's-related symptoms, although sleep quality appeared to worsen. They note that the patient considered the broader quality-of-life gains more important than the sleep trade-off. In discussing earlier work, the authors contrast this report with anecdotal accounts of ibogaine use in Parkinson's disease, which they say lacked structured baseline assessment with validated scales. They also relate the findings to proposed mechanisms from previous research, including GDNF-related effects, sigma-2 receptor activity, modulation of dopamine release, possible action at opioid receptors, and pharmacochaperone effects on the dopamine transporter. However, they acknowledge that the low dose used here was below doses previously associated with some of these biological effects, so other explanations may be needed. The main limitations they identify are the single-patient design, the absence of a control condition, and the very small sample size. They also suggest that response variability may reflect the heterogeneity of parkinsonism, including idiopathic, genetic, drug-induced, vascular, atypical, toxin-related and post-encephalitic forms. The authors conclude that future work should test ibogaine in double-blind, randomised, placebo-controlled crossover trials with adequate sample sizes, and if benefit is confirmed, investigate the underlying mechanisms further.
Ibogaine is the main indole alkaloid isolated from the root bark of the African shrub Tabernanthe iboga, which has played dual roles in the lives of West Equatorial African populations, i.e. in low doses as a stimulant and aphrodisiac or in higher doses for ritual purposes due to its hallucinogenic effects. It was marketed as an antidepressant in France for decades prior to withdrawal from market due political pressure. Since the 1960s a growing body of research supports the use of high-dose ibogaine for the treatment of substance use disorders, including medically supported legal off-label treatments for opioid dependence. More recent research has focused on the therapeutic potential for lower to medium doses of ibogaine to treat psychiatric conditions, including Post-traumatic Stress Disorder and traumatic brain injury. In addition to T. iboga, Voacanga africana has emerged as a more sustainable and accessible botanical source of ibogaine. A recent study has optimized the method for extracting voacangine, an ibogaine precursor, from V. africana root bark, demonstrating its viability as an alternative source. Furthermore, recent studies on ibogaine analogues, including Tabernantholog, oxa-iboga alkaloids, and related compounds, seek to maintain the therapeutic efficacy of ibogaine while minimizing associated cardiac risks and hallucinogenic properties. Despite these advances, such analogues are not widely studied and accessible yet. Anecdotal reports of ibogaine treatments of PD patients with favourable responses have emerged from 2014 onwards (Entheoscience, 2017 1/2; Entheoscience, 2017 2/2). However, none of these treatments reported systematic baseline evaluations with clinically validated rating instruments, which severely limits their value as observational evidence. The present case study reports the outcome for a PD patient treated with ibogaine hydrochloride and evaluated with standardized instruments. The female patient had been diagnosed with PD in 2006 at the age of 37. She was 52 years old at the time of treatment, with no comorbidities and reported no history of substance use disorder. Following receiving conventional treatment for PD consisting of Safinamide 100 mg 1x day, Ropinirol 24 mg 1x day and Levodopa/Carbidopa/Entacapone 100/25/200 mg 4-5 x day, all of which had ceased to be effective, the patient sought alternative treatment with ibogaine. She contacted the first author, who has previously consulted on the use of ibogaine as an adjuvant therapy for substance use disorders, PD and other conditions. The potential therapeutic use of low dose ibogaine to treat PD was discussed with the patient, who was fully informed about potential risks and consented to treatment, including assessment of treatment outcomes through collected data as well as publishing the data, with the understanding that the use of ibogaine was a non-standard treatment. Ethics: Prior to the commencement of treatment, the patient provided written informed consent for the treatment, collection of data and the details of her treatment to be published. During the 80-day treatment the patient continued taking her medication as described above, other than for Safinamide 100 mg 1x day, which she ceased taking for the first 12 days of the treatment. The rationale for pausing Safinamide was based on the fact that safinamide, as a monoamine oxidase B (MAO-B) inhibitor, may potentiate the effects of ibogaine. Consequently, a cautious approach to dosing was initially adopted. As treatment progressed satisfactorily, a mutual decision was made between the patient and the treatment provider to resume safinamide administration. In her baseline-assessment, the patient had clearly-pronounced Parkinson's Disease Symptoms. Despite being able to manage most of her daily life by herself, she perceived her condition as severe and progressively felt dependent on others. She reported feeling trapped in her body and impeded in the life she wanted to lead. She frequently suffered from off-phases i.e. freezing of gait and not being able to move for up to several hours a day, especially when wanting to initiate movement.
Before and after the treatment, the patient was evaluated with the following validated instruments: the Unified Parkinson's Disease Rating Scale (UPDRS;, a 42-item rating scale for assessing cognitive function, behavior and mood, thought disorders, depression, motivation, activities of daily living and language in patients with PD; the Parkinson's Disease Questionnaire-39 (PDQ-39;, a 39-item questionnaire that assesses PD-specific health-related quality of life; the Parkinson's Disease Sleep Scale-2 (PDSS-2;Following a baseline assessment of her PD symptomatology, the patient initially received 25 mg of ibogaine hydrochloride (containing 98.6% ibogaine HCl, obtained commercially and supplied with a certificate of purity) in one capsule, daily, every morning before food. This starting dose was selected as a cautious approach to assess individual sensitivity and minimize potential side effects, based on prior clinical observations indicating that doses below 25 mg/day are frequently subtherapeutic in patients with PD. Subsequently, in consultation with the treatment provider, the patient reviewed the dose weekly. This allowed for a patient-centered adjustment process guided by observed tolerance and therapeutic response. As a result, the dosing regimen was gradually increased, with the patient receiving up to a maximum of 75 mg (three capsules) per day, though a single dose never exceeded 50 mg (two capsules) at one time. This range (25-75 mg/day) reflects the provider's clinical experience with effective dosing for symptomatic relief in similar cases.
The outcomes for the patient, following the 80-day treatment with low dose ibogaine HCl are shown in Fig.. Marked improvements of negative symptoms were recorded for four of the five measures, i.e. the UPDRS, PDQ-39, PFS-16 and BDI-II all show reductions between the baseline measurement of symptoms and the conclusion of the ibogaine dosing regime at the end of 80 days. The exception to this trend is the PDSS-2 assessment quantifying the patient's level of sleep disruption, which shows a poorer outcome at the conclusion of the ibogaine treatment. During her treatment the patient was also encouraged to provide feedback on her response to the treatment regime. After two weeks of taking ibogaine and increasingly commented on by four weeks, she described improvements in her energy, flexibility and efficiency of movement, which she reported as having not experienced for years, and which at 80 days after commencing treatment with ibogaine she described as follows: In addition to alleviating the physiological symptoms of PD, the patient also reported increased energy levels and an improved mood:
To our knowledge this is the first case report using validated instruments to examine the impact of the therapeutic use of ibogaine on Parkinson's symptoms. The patient showed a pronounced reduction for negative symptoms on four of the five test scales (UPDRS, PDQ-39, PFS-16 & BDI-II), with the exception of the PDSS-2 (sleep scale), which indicated a deterioration in the patient's sleep. Other than for sleep quality, therefore, the data suggest that ibogaine may have the potential to alleviate a number of PD symptoms. In the present case these measured reductions in negative symptoms were supported by the patient describing her feelings of improvement in both physical and psychological aspects of her wellbeing. Ibogaine's stimulating effectsmay provide an explanation for the increase in sleep disruption. Of note, however, the patient reported that she felt that the overall improvement in her quality of life made the trade-off with reduced sleep quality worthwhile. She chose to prioritize the other reduced PD symptoms over a slightly better sleep quality. The treatment provider involved in the present case nonetheless reported their awareness of other PD patients displaying no response to ibogaine. In the personal experience of the treatment provider and in conversations with other treatment providers, it appears that approximately 40% of PD patients exhibit no therapeutic response to ibogaine; this variability in efficacy may be attributable to the heterogeneity of underlying causes of parkinsonism. These include, for example, idiopathic Parkinson's disease, genetic mutations (e.g., LRRK2, PARK7, PINK1, PRKN, SNCA), drug-induced parkinsonism, vascular parkinsonism, atypical parkinsonian syndromes (e.g., multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration), toxin exposure, and post-encephalitic parkinsonism. This highlights the limitations of the present report such as the minimal sample size and a non-controlled study design. At a physiological level, the potential therapeutic effects of ibogaine may be attributed to multiple mechanisms of action. However, as the upregulation of GDNF in the ventral tegmental areal and substantia nigra, as well as the increase of proBDNF (the precursor of brain-derived neurotrophic factor) in the nucleus accumbens, have been shown to require significantly higher doses of ibogaine (e.g., 20-40 mg/kg) than the dose described here, alternative models to explain the positive effects on PD patients are needed. One possible mechanism of action is the binding of ibogaine to the sigma-2 receptor. The synergy of GDNF and sigma-2 activation may play pivotal role in symptom improvement. Moreover the modulatory effects of ibogaine on dopamine release via sigma-2, NMDA and 5-HT3 receptors in striatal neurons could be attributed to symptomatic enhancement in PD patients. In addition, the affinity of ibogaine and noribogaine to various opioid receptors should be focused on in further research. This is especially the case since kappa-opioid agonists seem to increase the locomotor activity in monoamine-depleted rat models of parkinsonism. Another line of research highlights how parkinsonism and other pathological conditions are associated with mutations of the gene (SLC6A3), responsible for folding the Dopamine Transporter membrane protein (DAT). Pharmacological chaperones of DAT can be used to rescue misfolded proteins. Ibogaine and its metabolite, noribogaine, act as pharmacochaperones, especially for the folding-deficient DAT mutant proteins which give rise to parkinsonism. Additionally, there is evidence that ibogaine inhibits the homologous dopamine transporter (DAT) non-competitively by closing the extracellular pathway and stabilizing the inward-open state of the transporter. Since DAT is responsible for recycling dopamine after release, inhibitors of DAT will stop the reuptake of dopamine, causing prominent changes at the molecular, cellular, and behavioural levels. Furthermore, it has been shown that ibogaine increases the DAT surface expression. However, the patient in the present paper reported overall increase of cognitive functions and her brighter mood led to more motivation and positive energy in her daily life, which elevated her overall quality of life. This suggests that the antidepressant quality of ibogainepotentially plays an important role in the interrelated effects of ibogaine on PD symptoms. While it is also plausible that the improvement in mood was a secondary effect of enhanced physical functioning, clinical experience from the treatment provider indicates that in some cases, patients experience mood elevation even in the absence of measurable changes in motor symptoms. In certain instances, mood improvements have been reported to precede motor changes. Therefore, we consider it likely that ibogaine's impact on mood may result, at least in part, from its intrinsic antidepressant effects, rather than being exclusively a consequence of improved motor function. Since the present report describes a single case, future inquiries should evaluate the effect of ibogaine on PD symptoms in the form of double-blinded randomized placebo controlled cross-over trials with a large enough sample size to achieve statistical significance. In the case of evidence-based demonstration of therapeutic benefits, ibogaine's underlying mechanisms of action should be examined.
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