A March 2019 study published in Psychopharmacology tested the sub-acute and long-term effects of one inhalation of dried secretions from the parotid glands of the toad Bufo alvarius containing 5-MeO-DMT.1 Historically, this compound has been used for spiritual exploration and is gaining popularity for the treatment of mental health problems in a naturalistic setting. This study was done to learn more about the effects of 5-MeO-DMT on humans.
The study used 75 volunteers (60% male) with a mean age of 38 years.1 They represented the countries of the Czech Republic, Spain, and the Netherlands. The majority of volunteers (nearly 93%) had experience with psychedelics such as psilocybin and LSD. Fifteen reported they had no previous experience with 5-MeO-DMT whether from a toad, a plant, or synthetic. Dosing of volunteers was done in an outdoor location such as a garden, secluded location, or another natural setting. The exception was the participants in Spain who received their single dose in a house or tipi during the winter season.
The researchers gathered data (self-reported) on the mental health of the volunteers before the study began.
- 76.3% said they had no mental health disorder.
- 9.4% reported anxiety.
- 7.1% said they had an addiction problem.
- 2.4% said they were depressed.
- 2.4% reported having a personality disorder.
- 2.4% reported having another mental health disorder that was not listed.
The dried toad secretion was placed in a glass pipe and heated using a torch lighter. The volunteers were either standing or lying down when they inhaled the contents from the pipe. Facilitators instructed the participants to inhale as much vapor as possible and hold it for several seconds before exhaling. The facilitators chanted healing shamanic chants, played musical instruments or both while the participants had their experiences.
The actual amount of dried toad secretions measured into the glass pipes is unknown and an important limitation of the study. The authors said that none of the study facilitators weighed the dose of dried secretions before putting it in the pipe. Instead they “relied on visual inspection” of the individual doses. The study does not explain why there was no standardized dosing. After discussions with the facilitators, some estimated the dried secretions at 20 to 30 mg while others said they measured out 100 to 120 mg.
The volunteers completed a test battery of seven questionnaires before dosing, within 24 hours after dosing (either on-site or online), and at a 4-week follow up using an online questionnaire. The questionnaires were the Ego Dissolution Inventory (EDI), the 5-Dimensional Altered States and Consciousness Rating Scale (5D-ASC), the Satisfaction With Life Survey (SWL), the Depression, Anxiety, and Stress Scale 21 (DASS-21), the Five Facets Mindfulness Questionnaire (FFMQ-15), the Brief Symptom Inventory (BSI-18), and the Picture Concept Task (PCT).
Analysis of Toad Secretions
The researchers analyzed five samples of the toad secretions used in the study for the levels of 11 compounds. The ranges of each compound per 1 gram of dried secretion were:
- Tryptamines –
- 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) = 203.6 – 307.3 mg/g
- Bufotenin (5-HO-DMT) = 0.600 – 3.530 mg/g
- DET (N,N-dimethyltryptamine) = 0.415 µg/g (detected in only one sample)
- DMT (N,N-dimethyltryptamine) = 0.016 – 0.041 mg/g
- NMe-5-HT (N-methylserotonin) = 0.014 – 0.171 mg/g
- NMT (N-methyltryptamine) = not detected
- Steroid Lactones –
- Bufogenin = 0.005 – 0.013 mg/g (four samples)
- Bufotalidin = under the limit of quantification
- Tryptophols –
- 5-MeO-tryptophol (5-MTOH or 5-methoxytryptophol) = 0.696 – 3.053 µg/g
- 5-HO-tryptophol = not detected
- 5-MIAA (5-methoxy-3-indoleacetic acid) = not detected
It is not clear from the study description if these secretions were mixed together then administered to all the volunteers or if they represented samples from different testing locations.
Of the 75 study volunteers, 42 completed the questionnaires before dosing and within 24 hours of dosing.1 Twenty four completed the questionnaires for the 4- week follow up. The sub-acute and 4-week follow up results for each of the seven questionnaires as compared to the baseline data were as follows:
- EDI –
- The mean ego dissolution rating was 74.24. Most participants had a strong psychedelic experience after dosing.
- This rating is on a scale of 0-100 with zero being no ego dissolution and 100 being maximal dissolution.
- About 70% of the ratings were 60 to 100.
- 5D-ASC –
- The blissful state, spiritual experience, and experience of unity were the top three rated subscales in the test after dosing.
- The mean rating for the key-dimension of oceanic boundlessness was 65.8%.
- Oceanic boundlessness was highly rated by 60% to 100% of the respondents.
- Oceanic boundlessness ratings were positively correlated with ratings of SWL and negatively correlated with convergent thinking scores 24 hours after dosing.
- SWL –
- Satisfaction with life significantly increased within 24 hours of dosing.
- The enhanced satisfaction with life persisted into the 4-week follow up.
- After 24 hours, SWL scores positively correlated with scores on ego dissolution and oceanic boundlessness.
- DASS-21 and BSI-18 –
- Subjective ratings of depression, anxiety, and stress decreased 24 hours after dosing, but the changes were not statistically significant until four weeks later.
- Ratings of depression, anxiety, and stress were reduced 185, 39% and 27%, respectively after 24 hours. Statistical significance was achieved after four weeks at which point depression, anxiety, and stress ratings had decreased by 68%, 56%, and 48%, respectively.
- FFMQ-15 –
- Significant changes in the mindfulness parameters of non-judgment and awareness occurred four weeks after dosing.
- There were no significant changes in the sub-acute assessments of mindfulness.
- The data suggested changes in awareness were higher in the Dutch and Spanish volunteers.
- Picture Concept Test –
- The number of correct solutions chosen (a measure of convergent thinking) increased significantly after dosing and four weeks later.
- Convergent thinking scores were significantly higher in the Netherlands and Czech participants compared to those in Spain.
The authors concede that several uncontrolled variables in the study may have influenced the results.1 For example, the differences in convergent thinking scores by the country could be the result of toad secretion samples containing different components at different levels in samples at separate locations. This variability may also account for 30% of the study volunteers rating their psychedelic experience as low to medium. Controlling this variable could be accomplished by mixing and homogenizing the samples before dosing the participants.
Another uncontrolled variable was the lack of standardized doses and dosing regimen. As was explained earlier, facilitators “eyeballed” anywhere from 20 to 120 mg of dried secretions into the glass pipes of the participants. This introduces a considerable variability in the amount of 5-MeO-DMT and other potentially psychoactive components the participants received in the vapor. The authors calculated that for the main component, a participant received 30 -36 mg of 5-MeO-DMT if they received 120 mg dose of dried secretions. If their dose was around 30 mg, they received only 7.5 – 9.0 mg of 5-MeO-DMT. Other uncontrolled variables the authors pointed out were variations in inhalation techniques, and the amount of time the vapor was held in the lungs,
Although this study had significant limitations, the participants experienced enhanced life satisfaction and convergent thinking right after dosing which was maintained to the 4-week follow up. Increased ratings of mindfulness along with decreased anxiety, depression, and stress were seen after dosing. These effects increased over time and reached statistical significance at four weeks. Lower ratings of stress and depression and higher life satisfaction scores correlated with high levels of ego dissolution or oceanic boundlessness after dosing.
It is important to note that the parotid gland secretions of Bufo alvarius contain more compounds than just 5-MeO-DMT. Analysis of the secretions used in this study detected six additional compounds. It is unknown how these other compounds may be interacting with receptors and modifying the effects of 5-MeO-DMT, a phenomenon known as the entourage effect. Further studies are needed to understand the complex cocktail of chemicals in toad secretions. This understanding will lead to more effective therapies for treating a wider variety of conditions.