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Tuesday, April 16, 2024

Using Psychedelics During Pregnancy and Breastfeeding


No high-quality data is available to guide our understanding of the benefits and risks of psychedelic use during pregnancy. However, there are some good reasons to discuss psychedelic use in pregnancy or breastfeeding.

My aim was to review medical literature regarding psychedelics and pregnancy and report the results. There may be certain topics mentioned with one psychedelic and not another. This reflects the search’s findings rather than a decision to exclude certain psychedelics from some of the topics. My narrative is below. You can also find a discussion of these materials on the Psychedelic Medicine podcast with Dr. Lynn Marie Morski here

 

Why Consider Psychedelic Use in Pregnancy or while Breastfeeding?

Psychedelics are being studied with positive results for refractory mental health conditions and peri- or post-partum depression is common, undertreated, and without many good options. Psychotherapy or non-pharmacotherapy options may be ideal, although are not effective (enough) in many cases. There are risks to using drugs in pregnancy, yet there are also risks or potential for negative consequences associated with untreated mental illness. In essence, the risks taken to help a person get or stay well with a drug could be well worth the benefits in ability to connect, bond, and be attuned to their pregnancy or newborn, although is a sensitive and case by case decision to employ pharmacotherapy.

 

How Do Psychedelics Compare to Current Treatment Options?

There are a couple notable advantages [1]. The only FDA approved treatment for post-partum depression is a progesterone analogue that must be delivered over a 60-hour IV infusion and appears mildly efficacious. The invasive route of administration and prolonged infusion time are disadvantageous and would likely impede on a new mother’s ability to care or interact with their infant for an extended period.

Another attractive feature of psychedelic therapy is the intermittent nature of use, which would be advantageous in limiting exposure of drug to fetuses or newborns relative to chronic therapies. Common treatments for depression in pregnancy or post-partum depression include serotonin reuptake blocking antidepressants (SSRIs, SNRIs) which require daily administration. Use as a class in pregnancy may carry a small risk of increased autism spectrum disorders yet is controversial [2]. Some of these medications (paroxetine) have been associated with risks of birth defects or fussiness and agitation in breastfed newborns (fluoxetine).

Psychedelics could also have considerable risks. Beyond lack of safety data, medical approval, and regulation as illicit substances, psychedelics are powerful serotonergic compounds that have pleiotropic effects across immune, endocrine, and neural systems. These risks are likely more problematic during pregnancy than breastfeeding for at least a couple reasons. One is that a fetus is less developed than a newborn. Another is that if the infant is mature enough and mother’s milk supply robust enough then breaks from breastfeeding could minimize infant exposure.

 

Can Fetuses or Newborns be Exposed to Psychedelics if Ingested While Pregnant or Breastfeeding?

The answer is likely yes, although it’s not understood just how much exposure there is. Factors that influence placental transfer or ability to transfer to breast milk are determined by molecular size, lipid solubility, protein binding, and maternal drug concentration. Psychedelics are small molecules and fairly lipid soluble (most psychoactive drugs are due to need to cross the Blood Brain Barrier). Psilocybin, psilocin, and MDMA have been predicted and cited to be able to transfer to breast milk [1]. Therefore, it is reasonable to think that there would be infant exposure if ingested during pregnancy or during lactation for serotonergic psychedelics.

 

Neurodevelopment and Psychedelics

Serotonin and even endogenously produced psychedelics play important roles in neurodevelopment. It really does seem that serotonin is a ‘primordial’ type of neurotransmitter and is close to the heart of the mystery of life itself. Data is demonstrating that the endogenously occurring psychedelic N,N-dimethyltryptamines (DMT) can act as a neurotransmitter, neuromodulator, hormone, and immunomodulator itself and may play an important role in pregnancy and development [3]. This isn’t meant to imply that DMT is safe in pregnancy, as timing, concentration, and localized effects could all be key factors in biological processes it impacts.

Leading hypotheses for how psychedelics may give rise to either therapeutic actions or even adverse conditions such as Hallucinogen Persisting Perceptual Disorder (HPPD) involve neuroplastic effects of psychedelics [4]. Discussion of MDMA’s mechanism of action has also involved neurodevelopmental regression and reopening of ‘critical periods’. Fetuses and infants are already in highly neuroplastic states and undergoing rapid neurodevelopmental changes. Many psychedelics have been used in neurodevelopmental experiments using animals, however these oftentimes fall under scrutiny as not being translatable to humans. Therefore, it is unknown what effects exogenous psychedelics may have on these processes.

 

Ayahuasca and Mushrooms: Ritual Use of DMT and Psilocybin in Pregnancy

Ayahuasca, an oral brew containing harmala alkaloids and DMT has been consumed for centuries in pregnancy without any scientific publication of harms [5, 6]. Observational studies of adolescents that were exposed to ayahuasca at various stages of their development including in utero have found them normal from psychiatric and neuropsychological perspectives [5]. Psilocybin mushrooms grow in many species over the world and have also been reportedly used during pregnancy by anthropologic sources. Psilocybin and psilocin have a similar chemical structure to DMT. Lack of evidence is not the same as negative evidence, but it’s somewhat reassuring that there is little reported regarding problems with neurodevelopment with naturally occurring classic psychedelics like ayahuasca (DMT) or psilocybin despite historical ritual use.

 

 

MDMA: Pregnancy and Developmental Outcomes

Data from mothers that used MDMA during pregnancy have demonstrated impaired developmental outcomes, motor delays, and higher than average rates of birth defects [7-11]. Data from these studies tend to be confounded by heavy use of MDMA/ecstasy in conjunction with other substances (e.g., alcohol, tobacco), therefore may not be accurate representations of what risks of MDMA-assisted therapy in pregnancy or a lactating mother could be [12]. Nevertheless, MDMA can produce neurotoxic effects and is able to cross placental barriers, which may give considerable exposure to fetuses. Amphetamines, and likely MDMA, can concentrate in breast milk and be passed on to feeding infants. Pharmacokinetic models of pregnancy for other designer cathinones appear to indicate potential for harm [13].

 

LSD: Pregnancy and Birth Defects – Potential Teratogen?

There was early concern that LSD can cause chromosomal damage, but this has since been refuted in several experiments [14-18].  Data regarding teratogenic effects amongst animals has been controversial and reviewed in detail alongside what is known in humans [15]. It was concluded there is little good evidence that LSD is teratogenic or oncogenic despite having adequate exposure to the general population to observe these effects [15]. Nevertheless, several case reports of ophthalmic or limb abnormalities born to mothers who used LSD exist in medical literature [19-22]. There have been a couple of small case series document LSD use in pregnancy and normal birth outcomes, although these are not high quality or conclusive by any means [23]. Other drugs with ergoline structures are known to stimulate uterine contraction and have been used as abortifacients, but I have not been able to find cases of miscarriage in response to LSD use.

 

Ketamine: Post-Partum Depression Prophylaxis and Risks in Breastfeeding

There is surprisingly little data regarding the use of ketamine in pregnancy given its long standing medical availability, although older experiments have demonstrated the ability for ketamine to transfer across the placenta and stimulate uterine contractions early in pregnancy [24, 25]. A case report describes successful treatment of depression and uncomplicated term delivery of a newborn in a case of severe treatment-resistant depression with electroconvulsive therapy (ECT) and ketamine treatments [26]. Ketamine is sometimes used as a pain management agent in women giving birth by a C-section procedure. In this setting, several randomized trials suggest that use of ketamine in this setting can reduce prevalence and depressive symptom scores of post-partum women, although is associated with higher rates of emesis [27]. Analgesic pumps containing ketamine given for 48 hours after C-sections appeared to have better protective effects against depression than a single infusion during operation. A recent pharmacokinetic analysis of ketamine in four breastfeeding mothers provided data suggesting exposure to breastfeeding infants with subanesthetic dosing is minimal [28]. Overall, there is some animal literature supporting neurodevelopmental harms of ketamine exposure to fetuses, most clinical data from humans supports further research is necessary due to promising effects at preventing post-partum depression and potential compatibility with breastfeeding.

 

Endocrine Responses to Psychedelic Use

Pregnancy results in a changing body and much of the change occurs due to hormonal shifts in the endocrine system. The process of birth itself is also a highly orchestrated hormonal event. Psychedelics tend to cause temporary shifts in endocrine profiles including increased plasma concentration of cortisol, oxytocin, prolactin, and epinephrine [29]. They tend to have minimal effects on norepinephrine, testosterone, or progesterone [29]. It is unknown whether the hormonal changes induced by psychedelics are detrimental to pregnancy or lactation, or if they may be beneficial to infant bonding for cases of postpartum depression.

 

Set, Setting, and Pregnancy

It seems to be an important harm reduction consideration to think about dose and route of administration. Psychedelics can be intense experiences psychologically and sometimes physically also. Choices of experiences range from low doses of oral psychedelics (e.g., psilocybin, ayahuasca) to high doses of designer amphetamine psychedelics (MDMA) or short-acting tryptamines used via inhalation (5-MeO-DMT) or parenteral routes. I hypothesize that the way a psychedelic is used has large repercussions as to the ultimate risks that are being taken. I would think that more intense experiences from higher doses or routes of administration with shorter latency to onset carry higher risks. There’s also much that could be considered regarding the pregnancy itself as some are lower risk and uncomplicated whereas others are higher risk and have complications. This article is not meant to condone use of psychedelics in pregnancy, however one harm reduction tool in the event a psychedelic were ingested would be to choose a lower dose of an oral psychedelic containing a naturally occurring tryptamine such as psilocybin or ayahuasca. I cannot state that psychedelics are safe in pregnancy, but I would be relatively less concerned about an expecting mother drinking 25-50% of her usual ayahuasca dose opposed to taking 150mg of MDMA.  

 

Summary and Conclusions

Serotonergic psychedelics likely transfer across placental barriers as well as into breast milk. There is no high-quality data to inform persons about risks and benefits of psychedelic use during pregnancy. Recent literature has highlighted that psychedelic therapies may be advantageous or beneficial, particularly in cases of postpartum depression in which breastfeeding could be safely suspended to undergo use without exposing the baby.

 

Do you have any experience using psychedelics while pregnant or breastfeeding?

I’m happy to receive feedback or anecdotes at [email protected] 

 

Table 1. Psychedelics in Pregnancy and Breastfeeding









Psychedelic

Use in Pregnancy

Use in Breastfeeding

MDMA

Heavy use alone or in combination with other substances linked to developmental delays and higher rates of birth defects.

 

Capable of crossing placenta.

 

Transfers to breastmilk similar to other amphetamintes. May abstain from breastfeeding for 72 hours or 24 hours from negative urine test

Psilocybin/psilocin

Anthropologic use reported.

 

Likely capable of crossing placenta.

 

Transfers to breastmilk. May abstain from breastfeeding for 24-48 hours for safe use

Ayahuasca

Anthropologic use reported. Observational studies of exposed adolescents absent deficits.

 

Likely capable of crossing placenta.

Transfers to breastmilk. May abstain from breastfeeding for 24-48 hours for safe use

Ketamine

When utilized during C-section procedures it may prevent postpartum depression.

 

No studies available in pregnancy

Case series of four lactating mothers suggests relatively safe in lactation [28]

 

LSD

 

 

Concerns for teratogenicity largely refuted.

 

 Case reports of birth defects exist

Likely transfers to breastmilk. May abstain from breastfeeding for 48 hours for safe use

 

References

  1. Jairaj, C. and J.J. Rucker, Postpartum depression: A role for psychedelics? J Psychopharmacol, 2022. 36(8): p. 920-931.
  2. Mathew, S., et al., Role of Serotoninergic Antidepressants in the Development of Autism Spectrum Disorders: A Systematic Review. Cureus, 2022. 14(8): p. e28505.
  3. Jiménez, J.H. and J.C. Bouso, Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate. J Psychopharmacol, 2022. 36(8): p. 905-919.
  4. Calder, A.E. and G. Hasler, Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology, 2022.
  5. dos Santos, R.G., Safety and side effects of ayahuasca in humans–an overview focusing on developmental toxicology. J Psychoactive Drugs, 2013. 45(1): p. 68-78.
  6. Labate, B.C., Consumption of ayahuasca by children and pregnant women: medical controversies and religious perspectives. J Psychoactive Drugs, 2011. 43(1): p. 27-35.
  7. Singer, L.T., et al., Neurobehavioral outcomes of infants exposed to MDMA (Ecstasy) and other recreational drugs during pregnancy. Neurotoxicol Teratol, 2012. 34(3): p. 303-10.
  8. Singer, L.T., et al., One-year outcomes of prenatal exposure to MDMA and other recreational drugs. Pediatrics, 2012. 130(3): p. 407-13.
  9. Singer, L.T., et al., Developmental outcomes of 3,4-methylenedioxymethamphetamine (ecstasy)-exposed infants in the UK. Hum Psychopharmacol, 2015. 30(4): p. 290-4.
  10. Singer, L.T., et al., Motor delays in MDMA (ecstasy) exposed infants persist to 2 years. Neurotoxicol Teratol, 2016. 54: p. 22-8.
  11. Smid, M.C., T.D. Metz, and A.J. Gordon, Stimulant Use in Pregnancy: An Under-recognized Epidemic Among Pregnant Women. Clin Obstet Gynecol, 2019. 62(1): p. 168-184.
  12. Ho, E., L. Karimi-Tabesh, and G. Koren, Characteristics of pregnant women who use ecstasy (3, 4-methylenedioxymethamphetamine). Neurotoxicol Teratol, 2001. 23(6): p. 561-7.
  13. Strange, L.G., et al., The pharmacokinetic profile of synthetic cathinones in a pregnancy model. Neurotoxicol Teratol, 2017. 63: p. 9-13.
  14. Long, S.Y., Does LSD induce chromosomal damage and malformations? A review of the literature. Teratology, 1972. 6(1): p. 75-90.
  15. Cohen, M.M. and Y. Shiloh, Genetic toxicology of lysergic acid diethylamide (LSD-25). Mutat Res, 1977. 47(3-4): p. 183-209.
  16. Emerit, I., C. Roux, and J. Feingold, LSD: no chromosomal breakage in mother and embryos during rat pregnancy. Teratology, 1972. 6(1): p. 71-3.
  17. Jacobson, C.B. and C.M. Berlin, Possible reproductive detriment in LSD users. Jama, 1972. 222(11): p. 1367-73.
  18. Robinson, J.T., et al., Chromosome aberrations and LSD. A controlled study in 50 psychiatric patients. Br J Psychiatry, 1974. 125(0): p. 238-44.
  19. Chan, C.C., M. Fishman, and P.R. Egbert, Multiple ocular anomalies associated with maternal LSD ingestion. Arch Ophthalmol, 1978. 96(2): p. 282-4.
  20. Hoyt, C.S., Optic disc anomalies and maternal ingestion of LSD. J Pediatr Ophthalmol Strabismus, 1978. 15(5): p. 286-9.
  21. Margolis, S. and L. Martin, Anophthalmia in an infant of parents using LSD. Ann Ophthalmol, 1980. 12(12): p. 1378-81.
  22. Apple, D.J. and T.O. Bennett, Multiple systemic and ocular malformations associated with maternal LSD usage. Arch Ophthalmol, 1974. 92(4): p. 301-3.
  23. Aase, J.M., N. Laestadius, and D.W. Smith, Children of mothers who took L.S.D. in pregnancy. Lancet, 1970. 1(7663): p. 100-1.
  24. Ellingson, A., et al., Transplacental passage of ketamine after intravenous administration. Acta Anaesthesiol Scand, 1977. 21(1): p. 41-4.
  25. Oats, J.N., D.P. Vasey, and B.A. Waldron, Effects of ketamine on the pregnant uterus. Br J Anaesth, 1979. 51(12): p. 1163-6.
  26. Patel, A., et al., Safety and efficacy of ketamine-augmented electroconvulsive therapy in third trimester pregnancy complicated by COVID-19. Proc (Bayl Univ Med Cent), 2022. 35(6): p. 874-875.
  27. Li, Q., S. Wang, and X. Mei, A single intravenous administration of a sub-anesthetic ketamine dose during the perioperative period of cesarean section for preventing postpartum depression: A meta-analysis. Psychiatry Res, 2022. 310: p. 114396.
  28. Wolfson, P., et al., The Pharmacokinetics of Ketamine in the Breast Milk of Lactating Women: Quantification of Ketamine and Metabolites. J Psychoactive Drugs, 2022: p. 1-5.
  29. Liechti, M.E., Modern Clinical Research on LSD. Neuropsychopharmacology, 2017. 42(11): p. 2114-2127.



Dr. Jen Chalmers
Dr. Jen Chalmers
Dr. Jen Chalmers is an accomplished writer and cannabis enthusiast. With a Ph.D. in Botany and years of experience as a researcher, she brings a scientific perspective to her captivating articles on cannabis news, recipes, and the fascinating world of psychedelics.

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