Research question: What are the therapeutic potentials of MDMA and Ayahuasca
in treating mental illnesses.
1
Depression
Safety and Side Effects of Ayahuasca in Humans—An
Overview Focusing on Developmental Toxicology
 “A significant decrease in the scores of the Hamilton
Depression Scale was reported starting at 40 minutes
after ayahuasca intake.” (72)
The research from this study has suggested that even in very
small dosages (.5mg-1mg) ayahuasca has therapeutic effects.
What is also amazing is that the desired effects are achieved
within 40 minutes, were as conventional anti-depressants
can take up to 2 weeks to achieve there desired effects. The
only set back with this study is that it is small first clinical
trial. While it does have a double placebo, it does not have
other studies like it to support the findings.
Antidepressant Effects of a Single Dose of Ayahuasca in
Patients With Recurrent Depression
 “Administration of ayahuasca was associated with rapid
and sustained anti-depressive effects. Results were
similar across volunteers, regardless of the severity of the
current depressive episode.”
Promising that the results were consistent across
individuals and levels of depression. This evidence
suggests that ayahuasca does have anti-depressive effects
in reducing depression symptoms in patients with mild to
severe depression.
 “Ayahuasca was well tolerated. No significant
cardiovascular effects were observed after ayahuasca
intake, and vomiting was the only adverse effect
recorded. However, patients did not consider vomiting as
causing severe discomfort.”(79)
Very good evidence for the continuation of research on
ayahuasca. Since no extremely harmful effects were
witnessed it this study, it appears to relatively safe to
humans. This gives another reason to due larger research
on this topic and also helps prove that ayahuasca could
help medical potential since it does not appear to be
dangerous
 “Although described results are promising, because
treatment was not randomized or double-blind, and there
was no placebo or other comparator group, we cannot
conclude that the observed changes were in fact caused
by ayahuasca.” (80)
The main setback of this study is that it does not have a
randomized or double blind placebo. This could mean

that the changes could be cause by any number of things
outside reasons beside ayahuasca.
The research from the study found that “Increased blood
perfusion in the subgenual area, nucleus accumbens, and
insula were observed after ayahuasca intake.
Hypoactivation of these brain regions is usually
associated with depression, while increased activation is
usually associated with anti-depressive”(78). This finding
suggests that on region of the brain that are affected by
ayahausca consumption are the same regions of the brain
that are affected by depression and anti-depressive
effects.
The Potential Dangers of Using MDMA for
Psychotherapy
 “The period of mood activation induced by acute MDMA
is comparatively brief, typically around 5-6 hours.
Afterwards, there is a period of neurochemical depletion,
when feelings of anhedonia, lethargy, anger, and
depression can develop”(39)
MDMA should not be used for trying to treat depression.
Since depression is a lack of serotonin in the brain, taking
MDMA would cause your serotonin to deplete even
further then its already low amount. This could cause
depression to spike, or individuals who were in remission
to relapse.
 “Some recreational users also feel skeptical about their
drug-induced experiences: “Is the feeling of happiness
real or is it just from a pill”” (38)
This is not scientific research, but rather an anecdotal
piece of information. Even healthy users question the
feeling of happiness.
Erowid basic MDMA and Ayahuasca information
 MDMA Negative: post-trip Crash - unpleasantly harsh
comedown from the peak effect, mild depression and
fatigue for up to a week, severe depression and/or
fatigue (uncommon)
It appears that MDMA should not be used for trying to
treat depression. Because MDMA uses extremely large
amounts of dopamine and serotonin, the two
neurochemicals that people with depression have less of.
This results in a more severe post trip-crash as their
already low serotonin and dopamine become near
depleted. Also individuals with depression have a
problem producing serotonin and dopamine, therefore by
Research question: What are the therapeutic potentials of MDMA and Ayahuasca
in treating mental illnesses.
3
Anxiety
depleting those neurochemicals, it becomes extremely
hard to raise them back to healthy levels.
 Ayahuasca Positive: Mild to extreme mood lift, euphoria,
mentally therapeutic
This does not specify if that mood lift is sustained or not.
If the mood lift is only happening for a brief amount of
time, it could be more harmful then therapeutic.
 Ayahuasca Negative: Feeling as though one is dying or
losing one’s mind
Extremely negative side effect, could make the depression
worse, this effect is only recorded in a small amount of
people.
Antidepressant Effects of a Single Dose of Ayahuasca in
Patients With Recurrent Depression
 “Significant score decreases in HAM-D, MADRS, and
Anxious-Depression BPRS subscale scores were observed
during acute drug effects and from D1 to D21 and were
related to depressed mood, sadness, anxiety, feelings of
guilt, suicidal ideation, difficulties at work/activities,
pessimistic thinking, and difficulty concentrating.” (78)
Ayahuasca administration showed that over the course of
21 days, patients showed a decrease in anxiety as well as
depressed mood. Even though this study was focusing on
its effects on individuals with depression, it found that
ayahuasca could have therapeutic potential for treating
anxiety. This study could help give reason for another
study done on ayahausca effects on patients with anxiety
disorders.
The Potential Dangers of Using MDMA for Psychotherapy
 “ In a medical setting, found significant mood increases in
every positive mood state being assessed, including
emotional excitation and sensitivity. However, negative
moods were also boosted by MDMA, including
apprehensiveness anxiety, and fear-of-loss of thought
control. “(38)
This is the counter argument for using MDMA for treating
anxiety. The patient’s condition could worsen because of
the depletion of neurochemicals. Event though this is one
side effect, other conventional drugs like Xanax and
valium cause sedation, memory lose, drowsiness and
have extremely high addiction rates. When evaluating if
MDMA treatment for anxiety could be beneficial, it is
important to weight the pros against the cons.
 “While the drug was seen as an aid for therapy, they
explicitly suggested that the therapeutic element was the
core element. Furthermore, any therapeutic gains will
typically take a number of sessions over an extended time
frame.”(39)
As with any medicine we have now to reduce anxiety, it
usually takes 2-3 weeks to reach the desired effects. Also
MDMA is the only anti-anxiety type of medicine that does
induce a sedative effect like xanax or valium. With MDMA
assisted therapy sessions, patients could focus on therapy
more and slowly be taken off the drug.
How could MDMA (ecstasy) help anxiety disorders? A
neurobiological rationale
 “Fear conditioning and extinction has provided a
successful model for the development and treatment of
anxiety disorders (McNally, 2007; Myers, et al., 2007).
Extinction is not the same as erasure of fear memories;
rather, extinction is also an essential form of emotional
learning elicited by repeated exposure to safe but fear
evoking triggers in the absence of harmful consequences”
(389)
This could allow patients to relive extremely traumatic
experiences that would normally be unable to bear.
People with PTSD often report feeling emotionally
disconnected and unable to benefit from the supportive
presence of family and friends or therapists (likely
contributing to the development and maintenance of the
disorder).
 “first mechanism concerns the hormone oxytocin, which
is involved in trust and empathy and mediates the
anxiety- regulating effect of social closeness.” (390)
MDMA increases oxytocin levels (neurochemical that is
involved with trust and empathy and mediates the
anxiety- regulating effect of social closeness). It also
increases brain activity in the ventromedial prefrontal
cortex and the amygdala, which are the emotional
regulation part of the brain. And lastly releases
norepinephrine and cortisol which help with emotional
learning
PHENOMENOLOGICAL STUDY OF AYAHUASCA AND ITS
EFFECT ON ANXIETY
Research question: What are the therapeutic potentials of MDMA and Ayahuasca
in treating mental illnesses.
5


“All six participants reported significant reduction in
symptoms of anxiety, depression, and drug or alcohol
abuse as well as improvement in interpersonal
functioning and their ability to cope with stress. “(79)
During the ceremony all participants found it be a scary
or out control process. All participants reported
addressing core of challenging issues in their life, and
they all felt a part of something bigger or larger then
reality.
“Six participants reported that ceremonies could be scary,
hard, or out- of-control.”(81)
Even though there were negative effects, participants
considered this all part of the healing processes.
A Perhaps Unexpected Role of Norepinephrine in Actions of
MDMA
 “reboxetine pretreatment blocked increases in
“stimulated” interpersonal sensitivity and ratings of
anxiety—effects reasonably attributed to
norepinephrine.” (215)
The study administered reboxetine prior to the
administration of MDMA to see what role norepinephrine
played in the effects of MDMA. Reboxetine decreased
concentrations of norepinephrine in the blood; it also
increased blood pressure and heart rate. The most
intriguing finding is that the reboxetine reduced the
“high” feeling which was thought to be associated with
dopamine release.
PTSD
Erowid basic MDMA and Ayahuasca information
 MDMA Negative: inappropriate and/or unintended
emotional bonding, tendency to say things you might feel
uncomfortable about later
 Ayahuasca Negative: Fear and/or paranoia
The Potential Dangers of Using MDMA for Psychotherapy
 “MDMA assisted psychotherapy should initially be
explored not in patients whose psychiatric symptoms
originated with biological imbalances with possible
genetic components . . . but rather in patients who need
some assistance in process difficult emotions that have a
deep seated component of fear and/or anxiety. Two of
the main categories of patient who fit this description are
people suffering from Post Traumatic Stress Disorder
(PTSD), and people facing terminal illness” (39)
Because of the way the neurochemicals work in MDMA, it
is more reasonable to use MDMA for treating PTSD and
terminal illness. Also the effects you achieve during and
afterwards, including relieving disturbing or unpleasant
memories which is part of curing PTSD.
Durability of improvement in post-traumatic stress
disorder symptoms: a prospective long- term follow-up
study
 “Participants described the experimental treatment as
being helpful, sometimes dramatically so (“The therapy
made it possible for me to live”), but also as being difficult
at times (“one of the toughest things I have ever
done”).”(32)
 “The evidence we report in this LTFU study, conducted on
the average of nearly 3 1⁄2 years after the prior study’s
exit date, indicates that there was an enduring, clinically
meaningful benefit from MDMA-assisted psychotherapy
to PTSD patients.” (34)
 “two subjects had CAPS scores above 50 (13%), which
indicates relapse with moderate-to-severe PTSD
symptoms, which is above the cut-off for original study
entry.”(31)
Two patients ended up with worse PTSD then when the
study started. Even though this happened to only two
patients, the study was extremely small (only 19)
participants. Need to retest in a larger study, even
thought outside effects could have caused the relapse, in
a larger study with less outside variables, it would be able
to prove.
How could MDMA (ecstasy) help anxiety disorders? A
neurobiological rationale
 “Pharmaceutical compounds that acutely increase
norepinephrine may increase emotional activation
(Southwick, et al., 1999) and also enhance extinction
learning (Mueller, et al., 2008), but such compounds may
also temporarily increase anxiety in people with PTSD”
(390)
We need to way the pros against the cons. On one the
hand, it could help access deep seated memories of fear
that cause PSTD, but it could also cause an increase in
Research question: What are the therapeutic potentials of MDMA and Ayahuasca
in treating mental illnesses.
7

Other
anxiety of patients with PTSD having no medical benefits
and worsening their mental condition further.
“Consistent with increased oxytocin release, increased
closeness to others is regularly described following
MDMA administration” (390)
One of the suggest benefits of using MDMA in treating
PTSD is having it incorporated with therapy talk sessions.
This way is recommended because the neurochemical
oxytocin is associated with closeness to others. This could
give therapist an opportunity to form deeper connections
with the patients, deepening the trust between them. This
would allow more meaningful talk therapy because with
this deep level of trust would allow patients to talk about
about their deep seeded memories that are associated
with high levels of fear and stress.
Erowid basic MDMA and Ayahuasca information
 MDMA Positive: increased willingness to communicate,
decreased fear, feelings of comfort, belonging, and
closeness to others, forgiveness of self and others
 Ayahuasca Positive: Emotional healing, A sense of inner
peace and acceptance of self,
Safety and Side Effects of Ayahuasca in Humans—An
Overview Focusing on Developmental Toxicology
 “There is anecdotal evidence that ayahuasca has
therapeutic potential for treating several diseases
including substance dependence, depression and several
psychological disorders, and also for curing cancer” (72)
Even though there is not enough scientific research, the
anecdotal evidence gives reason for their to start being
scientific research done on ayahuasca.
 “There appears to be an overall good tolerability for longterm ayahuasca consumption.” (71)’
This is a good sign because with some conventional
medicines, dependence and addiction can form. Also it
has a significant effect on the mind and body. If ayahuasca
is relatively tolerable for long term use, it could already
by a better alternative medicine.
Source #3 Durability of improvement in post-traumatic
stress disorder symptoms: a prospective long- term followup study
 “Some of the areas of benefit that were endorsed on the
LTFU Questionnaire, such as an increased self-awareness,
improved relationships, an enhanced spiritual life, and
more involvement in the community or world, represent
effects that are not fully measured by the PTSD symptom
scale” (36).
MDMA could have more uses beyond treating PSTD. But it
also might not be as bad as the united states laws make it
out to be. With it effects compared to alcohol or tobacco,
it seems relatively safe to use recreationally, if not
medically.
PHENOMENOLOGICAL STUDY OF AYAHUASCA AND ITS
EFFECT ON ANXIETY

“All participants reported a significant reduction and, in
most cases, complete remission without reoccurrence of
symptoms of mild anxiety, phobias, depression, and drug
and alcohol abuse; increased ability to handle stress; and
improved overall health.” (83)
Ayahuasca users are experiencing a wide variety of
therapeutic effects. This opens up the possibility for my
research to be done. It also indicates that ayahuasca
might have therapeutic effects,
A Perhaps Unexpected Role of Norepinephrine in Actions of
MDMA
 “Earlier work demonstrated that citalopram
pretreatment attenuated most of the effects of MDMA,
including its effects on positive mood, derealization, and
thought disorder”(215)
This dissertation is suggesting that MDMA and
combination of other drug could be very beneficial to
achieve desired therapeutic effects, because of the role
norepinephrine plays in the brain.

“A very intriguing finding is that reboxetine attenuated
many of the amphetamine-like effects of MDMA, including
ratings of ‘high.’” (215)
If it reduces the high feeling, then it could allow patients
to focus more on the emotional side of effects, wonder if
this affects the day after effects?
Erowid basic MDMA and Ayahuasca information
 Ayahuasca Negative: Nausea, vomiting, diarrhea, body
aches, sweats/chills (alternating), and other flu- or food
poisoning-like symptoms
Research question: What are the therapeutic potentials of MDMA and Ayahuasca
in treating mental illnesses.
9