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other substances
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kratom

Mitragyna speciosa korth, also known by its Thai name, Kratom, is a tree native to southeast Asia. Its leaves have been traditionally used to treat fatigue, pain, opioid withdrawal, diabetes, and more. It is more commonly ingested as a tea or ground leaf powder, but can also be smoked. 

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Pharmacology

There is inconsistency in the literature regarding the mechanism of action, with disagreement even as to which receptors are bound to, and whether the effect is agonist or antagonist (1, 2, 3). The literature is consistent in reporting stimulant effects at doses <5 g, opioid-like effects at doses > 5 g (3-7), and absence of respiratory depression (1, 3, 4, 8-10). There are also reports of insulin-like effects in vitro (11), which may support traditional use as a treatment for diabetes.  Reported effects in humans include: pain relief, anxiety relief, antidiarrhea, antidiabetic, antileukemic, immunostimulant, antihypertensive, hyperpigmentation, dry mouth, polyuria, anorexia, dehydration, insomnia, diuresis, anti-inflammation, and constipation (2, 4, 7, 11).

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Treatment

Physiological dependence has been reported and patients were transitioned to buprenorphine/naloxone (Suboxone) (8, 12). Treatment is similar to that of opioid use disorder.

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Pregnancy
Fetus
Lactation

There are no reports in the literature of the effects experienced by pregnant or lactating people. There are several case reports of infants experiencing withdrawal signs after prenatal kratom exposure, however, almost all of them involved polysubstance use and chronic health conditions (1, 5, 6, 9, 13). The sole report of an infant prenatally exposed only to kratom finds inconclusive signs, such as irritability, excessive suck, and sneezing, which make diagnosis of neonatal withdrawal difficult. Morphine and subsequently clonidine dosing per protocol resulted in over sedation, and after 2 failed trials of medications, he spontaneously recovered and was sent home at 8 days (1).

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Overdose

There are many reports of morbidity and even mortality involving polysubstance use, but no reports of adverse effects from kratom use alone (3, 4, 7, 8, 19, 14-16).

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Withdrawal

Withdrawal signs and symptoms in adults are reported to be similar to opioid withdrawal, but milder and of longer duration.  These effects are mostly, but not always reported in the context of polysubstance use (8, 12, 15).

References:

1.    Eldridge, W. B., Foster, C., & Wyble, L. (2018). Neonatal Abstinence Syndrome Due to Maternal Kratom Use. Pediatrics, 142(6), e20181839. https://doi.org/10.1542/peds.2018-1839
2.    Hassan, Z., Bosch, O. G., Singh, D., Narayanan, S., Kasinather, B. V., Seifritz, E., Kornhuber, J., Quednow, B. B., & Müller, C. P. (2017). Novel Psychoactive Substances-Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs. Frontiers in psychiatry, 8, 152. https://doi.org/10.3389/fpsyt.2017.00152
3.    Toce, M. S., Chai, P. R., Burns, M. M., & Boyer, E. W. (2018). Pharmacologic Treatment of Opioid Use Disorder: a Review of Pharmacotherapy, Adjuncts, and Toxicity. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 14(4), 306–322. https://doi.org/10.1007/s13181-018-0685-1
4.    Fluyau, D., & Revadigar, N. (2017). Biochemical Benefits, Diagnosis, and Clinical Risks Evaluation of Kratom. Frontiers in psychiatry, 8, 62. https://doi.org/10.3389/fpsyt.2017.00062 
5.    Mackay, L., & Abrahams, R. (2018). Novel case of maternal and neonatal kratom dependence and withdrawal. Canadian family physician Medecin de famille canadien, 64(2), 121–122.
6.    Pizarro-Osilla C. (2017). Introducing… Kratom. Journal of emergency nursing, 43(4), 373–374. https://doi.org/10.1016/j.jen.2017.03.016 
7.    Prozialeck, W. C., Jivan, J. K., & Andurkar, S. V. (2012). Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. The Journal of the American Osteopathic Association, 112(12), 792–799.
8.    Boyer, E. W., Babu, K. M., Adkins, J. E., McCurdy, C. R., & Halpern, J. H. (2008). Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth). Addiction (Abingdon, England), 103(6), 1048–1050. https://doi.org/10.1111/j.1360-0443.2008.02209.x
9.    Murthy, P., & Clark, D. (2019). An unusual cause for neonatal abstinence syndrome. Paediatrics & child health, 24(1), 12–14. https://doi.org/10.1093/pch/pxy084
10.    Trakulsrichai, S., Tongpo, A., Sriapha, C., Wongvisawakorn, S., Rittilert, P., Kaojarern, S., & Wananukul, W. (2013). Kratom abuse in Ramathibodi Poison Center, Thailand: a five-year experience. Journal of psychoactive drugs, 45(5), 404–408. https://doi.org/10.1080/02791072.2013.844532
11.    Purintrapiban, J., Keawpradub, N., Kansenalak, S., Chittrakarn, S., Janchawee, B., & Sawangjaroen, K. (2011). Study on glucose transport in muscle cells by extracts from Mitragyna speciosa (Korth) and mitragynine. Natural product research, 25(15), 1379–1387. https://doi.org/10.1080/14786410802267627
12.    Smid, M. C., Charles, J. E., Gordon, A. J., & Wright, T. E. (2018). Use of Kratom, an Opioid-like Traditional Herb, in Pregnancy. Obstetrics and gynecology, 132(4), 926–928. https://doi.org/10.1097/AOG.0000000000002871 
13.    Davidson, L., Rawat, M., Stojanovski, S., & Chandrasekharan, P. (2019). Natural drugs, not so natural effects: Neonatal abstinence syndrome secondary to 'kratom'. Journal of neonatal-perinatal medicine, 12(1), 109–112. https://doi.org/10.3233/NPM-1863
14.    Anwar, M., Law, R., & Schier, J. (2016). Notes from the Field: Kratom (Mitragyna speciosa) Exposures Reported to Poison Centers - United States, 2010-2015. MMWR. Morbidity and mortality weekly report, 65(29), 748–749. https://doi.org/10.15585/mmwr.mm6529a4
15.    Cumpston, K. L., Carter, M., & Wills, B. K. (2018). Clinical outcomes after Kratom exposures: A poison center case series. The American journal of emergency medicine, 36(1), 166–168. https://doi.org/10.1016/j.ajem.2017.07.051
16.    Forrester M. B. (2013). Kratom exposures reported to Texas poison centers. Journal of addictive diseases, 32(4), 396–400. https://doi.org/10.1080/10550887.2013.854153

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Phencyclidine (PCP)

Phencyclidine (PCP) is classified as a schedule II drug. PCP was first manufactured in 1926 and was marketed and used as an anesthetic medication. Because of side effects and the availability of better alternative medication, its use was discontinued. PCP derivatives  have been sold for recreational and non-medical use. PCP usually comes as a white powder, which can be dissolved in alcohol or water. It can be bought as a powder or liquid. 

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Pharmacology

PCP is a dissociative anesthetic. (Journey 2020) It can be smoked, snorted, eaten, or injected. (Glantz 1993, Journey 2020) Effects are mildly stimulant and cause hypertension, tachycardia, bronchodilation, and agitation. (Journey 2020) It can also cause sedation. (Journey 2020) Higher doses cause ataxia, hypersalivation, and hallucinations, (Glantz 1993) or even seizure, coma, and death (Journey 2020). Half-life is estimated at 21 hours. PCP is fat soluble and can be released days to months after use. (Journey 2020)

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Treatment

Little is known about treating PCP use disorder.

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Pregnancy

There is very little recent research focusing on PCP in pregnant humans. Even in older studies, sample sizes are small and control for complicating factors is scarce. Neonatal treatments in the 1980s were very different from today, and in many cases included interventions which we now know to be harmful. (Strauss 1981, Howard 1986) Evidence in this section should be interpreted with caution.

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Fetus

PCP crosses the placenta. (Glantz 1993, Golden 1987) There is no evidence of a link with congenital anomalies, fetal loss, or preterm labor. (Glantz 1993) Infants in larger studies do not show any consistent effects. (Glantz 1993, Rahbar 1993, Wachsman 1989)

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Lactation

PCP is present in the milk of people who use it, (Howard 1998, LactMed, Reece-Stretman 2015) but infant effects are unknown (LactMed).

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Development

Chasnoff finds no differences in measurements or developmental scores, despite lack of control for maternal health and socioeconomic status. (Chasnoff 1983) PCP is present in the milk of people who use it, (Howard 1998, LactMed, Reece-Stretman 2015) but infant effects are unknown (LactMed).

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Overdose

Higher doses can cause seizures, coma, or death. (Journey 2020) PCP overdose is a medical emergency.

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Withdrawal

There is no evidence of dependence or withdrawal from PCP.

References:

  1. Chasnoff, I. J., Burns, W. J., Hatcher, R. P., & Burns, K. A. (1983). Phencyclidine: effects on the fetus and neonate. Developmental pharmacology and therapeutics, 6(6), 404–408. https://doi.org/10.1159/000457343

  2. Glantz JC, Woods JR Jr. Cocaine, heroin, and phencyclidine: obstetric perspectives. Clin Obstet Gynecol. 1993 Jun;36(2):279-301. doi: 10.1097/00003081-199306000-00009.

  3. Golden, N. L., Kuhnert, B. R., Sokol, R. J., Martier, S., & Williams, T. (1987). Neonatal manifestations of maternal phencyclidine exposure. Journal of perinatal medicine, 15(2), 185–191. https://doi.org/10.1515/jpme.1987.15.2.185

  4. Howard, C. R., & Lawrence, R. A. (1998). Breast-feeding and drug exposure. Obstetrics and gynecology clinics of North America, 25(1), 195–217. https://doi.org/10.1016/s0889-8545(05)70365-x

  5. Howard, J., Kropenske, V., & Tyler, R. (1986). The long-term effects on neurodevelopment in infants exposed prenatally to PCP. NIDA research monograph, 64, 237–251.

  6. Journey, J. D., & Bentley, T. P. (2020). Phencyclidine Toxicity. In StatPearls. StatPearls Publishing.

  7. LactMed Phencyclidine. (2018). In Drugs and Lactation Database (LactMed). National Library of Medicine (US).

  8. Rahbar, F., Fomufod, A., White, D., & Westney, L. S. (1993). Impact of intrauterine exposure to phencyclidine (PCP) and cocaine on neonates. Journal of the National Medical Association, 85(5), 349–352.

  9. Reece-Stretman, S. & Marinelli, K. A. (2015). ABM clinical protocol #21: Guidelines for breastfeeding and substance use or substance use disorder, revised 2015. Breastfeeding medicine. 10(3). 135-141.

  10. Strauss, A. A., Modaniou, H. D., & Bosu, S. K. (1981). Neonatal manifestations of maternal phencyclidine (PCP) abuse. Pediatrics, 68(4), 550–552.

  11. Wachsman, L., Schuetz, S., Chan, L. S., & Wingert, W. A. (1989). What happens to babies exposed to phencyclidine (PCP) in utero?. The American journal of drug and alcohol abuse, 15(1), 31–39. https://doi.org/10.3109/00952998908993397

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