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Ayahuasca: alkaloids, plants & analogs
assembled by Keeper of the Trout
Section 1 :
Modern studies of Ayahuasca users
Long-time ayahuasca users compared to well matched controls never having used ayahuasca

Note: In this usage ayahuasca refers to the drink (hoasca) containing harmine and DMT as the two primary active ingredients; the presence of tetrahydroharmine and/or lesser amounts of harmaline is also likely.

Ayahuasca users have been observed to show no apparent adverse health effects after 30 or more years of regular use. This issue was specifically studied using both long term regular drinkers of ayahuasca and well matched controls within the same community. Long-time users showed a superior performance on a neuropsychological test that was designed to assess attention, memory, recall and verbal ability (WHO-UCLA Auditory Verbal Learning Test). Differences were also noted in a personality profile using the Tridimensional Personality Questionnaire (TPQ). While there were no differences seen on the Reward Dependence dimension, positive increases were noted in both the harm avoidance category and the novelty seeking scale.

TPQ Category
UDV members showed greater:As opposed to:
 
Harm Avoidance
ConfidenceFear of uncertainty
GregariousnessShyness with strangers
Uninhibited optimismAnticipatory worry
VigorFatigability and asthenia
  
Novelty Seeking
Stoic rigidityExploratory excitability
RegimentationDisorderliness
ReflectionImpulsiveness

    McKenna & Grob 1994 (See full details in Grob et al. 1996)

A significant degree of past psychopathology (including alcoholism, depression and violence) that existed prior to UdV involvement were reported to have resolved without occurrence following their involvement with ayahuasca (and the UdV). McKenna & Grob 1994 & Grob et al. 1996

Interestingly, many long term ayahuasca drinkers had reported a discontinuation of pre-existing alcoholism and/or violent behaviors after becoming involved with the UdV and a deficit of 5-HT receptors in the frontal cortex has been linked to aggression disorders in alcoholics. The significance and potential for treating such aggression disorders is presently unclear but intriguing.
    [McKenna et al. 1998 citing Callaway et al. 1994]

Grob et al. 1996 noted that the remission of pre-existing psychopathology following their use of ayahuasca showed no evidence of either personality or cognitive deterioration.

A "significant up-regulation in the density of the citalopram binding sites" was reported in hoasca drinkers when compared to well matched control subjects.
    [McKenna et al. 1998 citing Callaway et al. 1994]

When Callaway ran SPECT scans of his own brain following 6 weeks of daily THH ingestion he found that the density of central 5-HT receptors in his prefrontal cortex had increased. After discontinuing the THH administration he reported a return to normal levels over the course of the next several weeks.

Dennis J. McKenna & Charles S. Grob hypothesized that hoasca acts primarily as a serotonergic agonist. They used blood platelets as peripheral markers reflecting changes in the central nervous system. They found an increased density of binding sites (serotonin receptors) in the platelets of long-time ayahuasca users.

While many drugs are known which decrease them, no other agent except for the aging process is known to increase serotonin platelet receptors. McKenna & Grob 1994 postulated that this might reflect the wisdom observed in the long term ayahuasca users and with healthy aged individuals generally.

Cortisol and prolactin levels both were observed to increase rapidly following the ingestion of hoasca according to McKenna & Grob 1994. [Both were also noted to increase following administration of pure DMT. See Strassman & Qualls.]

While comparable to the results of Strassman & Qualls 1994, using injected DMT fumarate, the responses to ayahuasca were delayed by a time factor of 4 to 5.

Pupillary diameter increased from 3.7 mm to ~4.7 mm at 40 minutes after ingestion and remained dilated at 240 minutes after ingestion (the last measurement that was taken)

There was also an increase in breaths per minute, and a slight rise in body temperature. Heart rates showed a similar increase (peaking at 20 minutes following ingestion and returning towards normal at 240 minutes) as did blood pressure (peaking 40 minutes after ingestion and returning to baseline by 180 minutes after ingestion)

Prolactin, cortisol and growth hormone all showed dramatic and rapid increases over baseline. The time course they reported for this increase (following hoasca ingestion) was 60 minutes for cortisol, 90 minutes for growth hormone and 120 minutes for prolactin.
    McKenna et al. 1998 cited Callaway et al. 1997]

The hoasca b-carbolines function as MAOIs at approximately a 10nM concentration.

The primary action of the harmala alkaloids is believed to involve their inhibition of peripheral MAO-A.

However, DMT has been reported to be primarily oxidized by MAO-B by Suzuki et al. 1981. This work suggests that the b-carbolines may also inhibit MAO-B partially but that tyramine has a greater affinity for MAO-B and can therefore competitively displace it; explaining the apparent lack of hypertensive crises when tyramine containing food are ingested following ayahuasca. [It was shown by Callaway & McKenna that MAO-B inhibition could in fact occur at the levels ingested by humans drinking ayahuasca)

THH may act as a weak 5-HT uptake inhibitor and MAOI. Or THH may prolong the half-life of DMT by blocking its reuptake and preventing its inactivation by the MAO located within the neuron in the mitochondria.

Or it may block the reuptake of serotonin into the neuron thus resulting in a higher level of serotonin within the synapse which may "attenuate the subjective effects of orally ingested DMT by competing with it at post-synaptic receptor sites".
    McKenna et al. 1998

Harmala alkaloids are highly selective MAO-A inhibitors (The version of MAO that uses serotonin as its preferred substrate.) [See comments elsewhere here about limited MAO-B inhibition]

Besides being competitive, reversible MAO-A inhibitors, the hoasca b-carbolines have been reported to competitively inhibit the uptake of 5-HT, dopamine, epinephrine & norepinephrine, inhibit the Na+ dependent membrane ATPases, interfere with biosynthesis of biogenic amines and exert vasopressin-like effects on sodium and water transport.
    McKenna et al. 1998

Callaway's results following the ingestion of UdV hoasca tea by humans (from McKenna et al. 1998):

  • Onset in 35-40 minutes.
  • Duration around 4 hours


CompoundDosageMaximum
plasma level
Time to reach maximumHalf-life
DMT0.48 mg/kg15.8 ng/ml107 minutes259 minutes
THH2.14 mg/kg91 ng/ml174 minutes532 minutes
Harmaline0.40 mg/kg6.3 ng/ml145 minutesNot measurable
Harmine3.40 mg/kg114.8 ng/ml102 minutes115.6 minutes



Interestingly, only 12 out of their 15 UdV volunteers showed adequate plasma levels of DMT to permit pharmacokinetic measurements. They speculated this may have been from the other subjects vomiting early during the session.

Note that 14 of the 15 had evaluable levels of THH)

For pharmacological and/or physiological studies, see:
  • Callaway & Grob 1998 [from McKenna et al. 1998]
  • Callaway & McKenna 1998
  • Callaway et al. 1994
  • Callaway et al. 1996
  • Callaway et al. 1997 [from McKenna et al. 1998]
  • Callaway et al. 1998 [from McKenna et al. 1998]

Common names, and some associated words.

  • Canessa et al. 1973
  • Don et al. 1998
  • Fuentes & Longo 1971
  • Grob et al. 1996
  • de Sousa & Grosso 1978

EEG studies:
  • Electroencephalograms of Ecuadorian Shuar shamans before and during ayahuasca.
      Fericgla 1997

    EEG studies indicated an increase in the activation of the visual cortex:

    "We observed increases in power in the 36-44 Hz frequency band ("40 Hz") from the left occipital-temporal-parietal scalp electrodes in the eyes closed-condition, which extended to most of the posterior scalp in the eyes-open condition." They also "noted tendencies towards decreases in the power of slow (theta and alpha) brain rhythms, and increases in the 14-30 Hz beta band, in accord with studies reported 30 years ago with other consciousness-altering compounds."
      Don et al. 1998

    Review:
  • McKenna et al. 1998

  • Psychological effects and applications of ayahuasca:
  • Fericgla 1997
  • Grob et al. 1996
  • Naranjo 1987
  • For Religious uses:
  • Ott 1993 (or 1996) and references therein. See also
  • Fericgla 1998 and Verlangieri 1998.
  • Also:
  • Beneficente União do Vegetal (1989) União do Vegetal. Hoasca: Fundamentos e Objetivos.
  • Edward MacRae (1992) Guiado Pela Lua: Xamanismo e Uso Ritual da Ayahuasca no Culto do Santo Daime.