Are Psychedelics Contraindicated in Raynaud’s Syndrome?

Big appreciation for this guest blog post which was written and contributed by Drug Information Pharmacist Dr. Erika Beerbower PharmD

Dr. Erika Beerbower (she/her), PharmD, is a practicing drug information pharmacist with 16 years of experience as a Clinical Content Specialist. She has a diverse background in content creation and literature analysis, blockchain technology, cannabis science, pharmacogenomics, and psychedelic pharmacy. She is a member of the Psychedelic Pharmacists Association and has a passion for harm reduction and education in the psychedelic space.

What is Raynaud's Syndrome?

Raynaud’s Syndrome (RS) is a vasospastic condition that is characterized by a disorder of thermoregulation in selected areas (primarily fingers and toes; although nose, toes, and nipples can also be affected), where unique arterial and venous systems help control temperature [1].  Persons with RS experience exaggerated vasoconstriction [2] resulting in reversible but sometimes painful episodic attacks, lasting 15 to 20 minutes. The affected extremity skin turns white indicating ischemia [in some cases with progression to blue (pallor), and then red (reperfusion)] and becomes tingly and numb. Attacks are caused by environmental stressors (exposure to cold) or emotional factors (e.g., anxiety). The incidence of RS in the general population is 10%; incidences up to 30% have been reported in colder climates and in younger females [3]. Primary RS, the most common type, is idiopathic, whereas secondary RS involves an underlying disease (e.g., systemic autoimmune rheumatic diseases). Mechanisms that may contribute to RS include exaggerated vasoconstriction, reduced blood flow, and immune, inflammatory, and neurogenic responses [4]; recent research has suggested a genetic component to RS.  There is usually no long-term health consequences associated with primary RS; however, secondary RS may be associated with tissue damage. Preliminary data from one study suggests a possible increased risk of cardiovascular disease in those with RS; however, further research is needed to confirm these findings [5].

What Medications are Contraindicated in Raynaud’s Syndrome?

Medications with warnings in the product labeling of worsening or inducing RS include ergot alkaloids, stimulants, clonidine, beta-blockers, calcitonin gene-related peptide (CGRP) receptor antagonists, dopamine agonists, chemotherapy, sympathomimetics and interferon [6]. In a study that analyzed the FDA adverse reporting system, 68 medications were linked to RS [7].

Ergot alkaloids such as ergotamine and dihydroergotamine for the treatment of cluster headaches and migraines are known to cause peripheral vasoconstriction, mainly via stimulation of 5HT2 receptors, and to a lesser extent alpha-2 adrenergic and dopamine-2 (D2) receptor agonism. In rare cases “ergotism” has been reported, leading to gangrene from prolonged vasoconstriction.

Stimulants such as amphetamine and its derivatives, commonly for the treatment of ADHD, have also been implicated in RS; these medications release or inhibit the reuptake of catecholamines (norepinephrine and dopamine) which contribute to increased vasoconstriction. In a genome-wide association study in RS, the role of the alpha-2a adrenergic receptor was highlighted as responsible for catecholamine induced vasoconstriction in small arteries and arterioles.[8] RS has been reported in pediatric patients receiving dextroamphetamine or methylphenidate in several small studies [9] [10] [11]. Case reports of RS also include the norepinephrine reuptake inhibitor atomoxetine[12], sympathomimetics such as phentermine[13], and the alpha2 adrenergic agonist clonidine [14].

How do Medications Contraindicated in Raynaud’s Syndrome Compare with Psychedelics?

Tryptamine psychedelics including LSD, psilocybin, DMT, and 5-Meo-DMT all stimulate the 5HT2A receptor [15] [16]. As noted with ergot alkaloids, 5HT2 receptor binding on smooth muscle cells in peripheral blood vessel walls has known vasoconstrictor effects [17]. LSD, originally derived from ergot fungus [18], has both tryptamine and phenylethylamine properties. Receptor targets of LSD include stimulation of 5HT2A, D2, and alpha 2a [19], all of which share mechanisms of medications that may worsen RS.

The phenethylamine MDMA stimulates 5HT2A receptors and releases serotonin via inhibition of VMAT2, and to a lesser extent causes release and inhibits reuptake of norepinephrine and dopamine.[20] In this case, multiple mechanisms are present that may increase vasoconstriction, making MDMA a potential concern for patients with RS. Worsening of RS due to vasoconstriction may occur with psychedelics that bind to 5HT2A, D2, alpha 2a, or with catecholamine release or reuptake inhibition.

What are Tips and Suggestions for Managing Raynaud’s Syndrome with Concomitant Psychedelics?

While psychedelics are not strictly contraindicated in RS, an attack could be induced during a journey. If proceeding, consider overlapping mechanisms that contribute to vasoconstriction (including other medications)6. Avoid nicotine (a vasoconstrictor known to worsen RS) [21]  and consider set and setting. It is important to stay warm4, including use of hot packs, heated blankets, and warm layers for extremities. Avoid air-conditioned spaces and cold weather.  Warming hands in hot water every 4 hours may be a preventative measure for patients with RS according to a small study [22]. Since RS can also be induced by emotional factors [23], it is important to note that a cold environment is not always the culprit for an attack. Emotional ups and downs during a psychedelic journey may worsen (or even improve) symptoms of RS.

High Points

RS is not a contraindication to undergoing a psychedelic journey; however, there are mechanisms inherent to serotonergic psychedelics that may aggravate or induce RS. Tools that may help prevent or minimize attacks or provide comfort during a journey include a comprehensive intake, including the type of RS and history of attacks, concomitant medications or conditions on board that may worsen or contribute to RS, and awareness of environmental and emotional triggers hallmark to this syndrome.

Do you have something to share regarding your experiences with psychedelics and Raynaud's Syndrome? Feel free to drop us a line at [email protected] 

References

[1] Flavahan NA. A vascular mechanistic approach to understanding Raynaud phenomenon. Nat Rev Rheumatol. 2015 Mar;11(3):146-58. doi: 10.1038nrrheum.2014.195. Epub 2014 Dec 23. PMID: 25536485.

[2] Fardoun MM, Nassif J, Issa K, et al; Raynaud's Phenomenon: A Brief Review of the Underlying Mechanisms. Front Pharmacol. 2016 Nov 16;7:438. doi: 10.3389/fphar.2016.00438.

[3] Belch J, Carlizza A, Carpentier PH, et al. ESVM guidelines - the diagnosis and management of Raynaud's phenomenon. Vasa. 2017 Oct;46(6):413-423. doi: 10.1024/0301-1526/a000661.

[4] Musa R, Qurie A. Raynaud Disease. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499833/

[5] Hughes M, Ruaro B, McMahan ZH, et al. Raynaud's phenomenon is associated with an increased risk of cardiovascular disease and venous thromboembolism. Semin Arthritis Rheum. 2025 Oct;74:152799. doi: 10.1016/j.semarthrit.2025.152799.

[6] Khouri C, Blaise S, Carpentier P, et al. Drug-induced Raynaud's phenomenon: beyond β-adrenoceptor blockers. Br J Clin Pharmacol. 2016 Jul;82(1):6-16. doi: 10.1111/bcp.12912.

[7] Zheng, P., Zheng, X., Chen, Q. et al. A comprehensive study on drug-related Raynaud’s phenomenon based on the FDA adverse event reporting system. Sci Rep 15, 32059 (2025). https://doi.org/10.1038/s41598-025-17182-z

[8] Hartmann S, Yasmeen S, Jacobs BM, et al. ADRA2A and IRX1 are putative risk genes for Raynaud's phenomenon. Nat Commun. 2023 Oct 12;14(1):6156. doi: 10.1038/s41467-023-41876-5

[9] Syed RH, Moore TL. Methylphenidate and dextroamphetamine-induced peripheral vasculopathy. J Clin Rheumatol. 2008 Feb;14(1):30-3. doi: 10.1097/RHU.0b013e3181639aaa.

[10] Laboe C, Batchelder E, Vasireddy D. Persistent Raynaud's Phenomenon Following Methylphenidate Hydrochloride Use During the COVID-19 Pandemic. Cureus. 2021 Sep 1;13(9): e17647. doi: 10.7759/cureus.

[11] Umair HM, Sandler RD, Alunno A, et al. Association between central nervous system stimulants used to treat attention deficit hyperactivity disorder (ADHD) and Raynaud's phenomenon: A scoping review. Semin Arthritis Rheum. 2021 Dec;51(6):1200-1204. doi: 10.1016/j.semarthrit.2021.09.002

[12] Gökçen C, Kutuk MO, Coşkun S. Dose-dependent Raynaud’s phenomenon developing from use of atomoxetine in a girl. J Child Adolesc Psychopharmacol 2013; 23: 428–30.

[13]  Jefferson HJ, Jayne DR. Peripheral vasculopathy and nephropathy in association with phentermine. Nephrol Dial Transplant 1999; 14: 1761–3.

[14] Winchester JF, Kennedy AC. Iatrogenic Raynaud's phenomenon. Br Med J. 1971 Jul 10;3(5766):113. doi: 10.1136/bmj.3.5766.113-b.

[15] Glennon RA, Teitler M, Sanders-Bush E. Hallucinogens and serotonergic mechanisms. NIDA Res Monogr. 1992;119:131-5

[16] McClue SJ, Brazell C, Stahl SM. Hallucinogenic drugs are partial agonists of the human platelet shape change response: a physiological model of the 5-HT2 receptor. Biol Psychiatry. 1989 Jul;26(3):297-302. doi: 10.1016/0006-3223(89)90042-5.

[17] Yildiz O, Smith JR, Purdy RE. Serotonin and vasoconstrictor synergism. Life Sci. 1998;62(19):1723-32. doi: 10.1016/s0024-3205(97)01166-1. PMID: 9585103.

[18] Nichols DE. Psychedelics. Pharmacol Rev. 2016 Apr;68(2):264-355. doi: 10.1124/pr.115.011478. Erratum in: Pharmacol Rev. 2016 Apr;68(2):356. doi: 10.1124/pr.114.011478err.

[19] Passie T, Halpern JH, Stichtenoth DO, et al. The pharmacology of lysergic acid diethylamide: a review. CNS Neurosci Ther. 2008 Winter;14(4):295-314. doi: 10.1111/j.1755-5949.2008.00059.x.

[20] MAPS. MDMA Investigator's Brochure, 11th edition. 2019; Available from: https://mapscontent.s3-us-west-1.amazonaws.com/research-archive/mdma/MDMA-Investigator-Brochure-IB-11thEdition-MAPS-2019-07-10.pdf

[21] Jackson CM. The patient with cold hands: understanding Raynaud's disease. JAAPA. 2006 Nov;19(11):34-8. doi: 10.1097/01720610-200611000-00006.

[22] Goodfield MJ, Rowell NR. Hand warming as a treatment for Raynaud's phenomenon in systemic sclerosis. Br J Dermatol. 1988 Nov;119(5):643-6. doi: 10.1111/j.1365-2133.1988.tb03477.x.

[23] Fábián B, Csiki Z, Bugán A. Alexithymia and emotion regulation in patients with Raynaud's disease. J Clin Psychol. 2020 Sep;76(9):1696-1704. doi: 10.1002/jclp.22947.