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Tools to Reduce Withdrawal, Cravings & PAWS

Tools to Reduce Withdrawals, Cravings & PAWS
  • Tools for addressing physical symptoms of withdrawal, cravings or PAWS when tapering, switching, detoxing, or nourishing post-detox.

Nourishing the Body in Withdrawal

This guide is intended primarily to help people in recovery by providing practical and accessible tools to reduce physical dependency to opioids, stimulants, and alcohol. So much of addiction treatment focuses on groups and spiritual counseling, but neglect the body and the physical challenges of recovery. The philosophy behind the list below is facilitating the reduction of tolerance and the production of endogenous neurotransmitters, thereby assisting with dose tapering, reducing withdrawal, and mitigating long-term post-acute withdrawal symptoms (PAWS), cravings and depression.

These tools are things that can be also helpful for people undergoing ibogaine treatment. While ibogaine is uniquely effective at reducing accumulated tolerance and people do generally experience a dramatic reduction in withdrawal, cravings, PAWS and post-treatment depression, these things are often not eliminated completely. In my view, it’s critical to think about the recovery process with ibogaine as a long-term process, not as an overnight event. Regardless of whether or not you are using ibogaine, but even if you are, this list includes resources that can be important at various stages of recovery.

The approach of decreasing tolerance is counter to the current public health logic in opioid addiction treatment that often seeks to maintain tolerance through long-term opioid maintenance in order to avoid the risk of overdose in the case of a relapse. That being the case, there is a risk in using ibogaine and these other methods that reduce tolerance. Sensitizing the dopamine system concurrently with the use of substance can deepen and entrench dependence, or in some cases precipitate overdose. If you use opioids after detoxing with ibogaine or these other methods you need to take into consideration that your sensitivity will be increased and take a lower dose than you have been accustomed to taking.

Some of these resources are available over the counter at health food stores or other specialty shops or clinics. Many of these things are commonly accessible online. In some cases, however, where I haven’t found sufficient options, I make some things available directly. When considering any of these options you are welcome to either schedule an orientation call or call +1 (888) 848-7972.

Disclaimer: None of these statements below have been reviewed by the FDA and have not been verified through clinical trials. Some of these are drawn simply from my own personal experience over the past ten years working in ibogaine-assisted recovery, as well as from the shared experience of many others. The majority of these options have been explored and studied on their own to some extent, and as much reference material as possible is linked. However, acknowledging that they may have limited effectiveness, these methods should be considered either together in combination, or complimentary to other conventional methods, and this should not be considered as a replacement for medical advice.

These recommendations can cause interactions or have synergistic effects with other substances. Taking this into consideration it is highly recommended to discuss these options with your doctor.

Kratom

Kratom is a tropical evergreen tree that is indigenous to Southeast Asia. Its leaves have a history of use in traditional medicine, particularly for the treatment of pain. While it is not an opiate, kratom acts as an agonist on several opioid receptors, providing pain relief and other benefits.

Some people have found that switching to kratom from other opioids helps to dramatically reduce withdrawal. While not quite as severe, regular use of kratom can lead to dependency and withdrawal symptoms. Some people have sought out ibogaine treatment specifically for long-time kratom dependence, however its use may provide some benefits, particularly in preparation.

Kratom for Opioid Withdrawal

Some find that switching from regular opioid use to kratom has led to a relatively stable switch without experiencing the majority of withdrawal symptoms. Theoretically, if this switch is done for a period of a few weeks, prior to developing a tolerance for kratom, then the kratom can be tapered and stopped with relatively little discomfort. In addition to some of the complimentary approaches below, this may provide a relatively safe, as well as legal and economically stable alternative for if you are accessing opioids illegally.

Kratom for Pre-Ibogaine Treatment

People who are planning to detox with ibogaine but are taking long-acting opioid maintenance medications like methadone or suboxone are frequently instructed to switch to a short acting opioid for periods often ranging from four to six weeks or longer. Some people have found their only option is to switch to short-acting prescription opioid medications, or illegal sources. Kratom provides an alternative that is legal in all but six US states, thereby avoiding destabilizing life-style changes after maintenance treatments.

Ceiba has designed a pre-treatment Stable Prep Kratom Kit designed to accommodate a week of regular use (every four hours). The kit is equipped with morning, afternoon and evening blends to help manage daytime energy and sleep, as well as with extracts designed to boost effectiveness in avoiding withdrawal symptoms. Learn more about this option.

Please note that mitragynine, the primary bioactive compound in kratom, can produce some similar cardiac effects as ibogaine,1Lu, J., Wei, H., Wu, J., Jamil, M. F., Tan, M. L., Adenan, M. I., Wong, P., & Shim, W. (2014). Evaluation of the cardiotoxicity of mitragynine and its analogues using human induced pluripotent stem cell-derived cardiomyocytes. PloS one, 9(12), e115648. https://doi.org/10.1371/journal.pone.0115648 and that ibogaine should not be used immediately following kratom use. In most cases stabilizing off of kratom should take place for at least four days prior to ibogaine detox and additional cardiac screening should be conducted as needed. Please discuss this additional stabilization period with your treatment provider. Even with this additional time, kratom provides a useful option for those who otherwise need to switch off of methadone or suboxone for 4-6 weeks.

Kratom for Post-Ibogaine Detox

Just to clarify, I do not recommend kratom for managing withdrawals, cravings or PAWS after detoxing with ibogaine. As mentioned above, it is possible to accumulate a tolerance to kratom and experience withdawal, which some people have sought ibogaine treatment for. This is counter to the general philosophy behind this guide of re-sensitizing the body. If you are looking for additional tools after ibogaine treatment I highly recommend using the other methods outlined below.

Herbal Assist

Herbal Assist is a mixture of twenty different herbs used in Traditional Chinese Medicine (TCM). It is an adapted version of the Heantos formula, which has been researched for the purpose of assisting in opioid withdrawal, reduction of cravings, and sedation.2Brodeur, C., Montplaisir, J., Godbout, R., & Marinier, R. (1988). Treatment of restless legs syndrome and periodic movements during sleep with L-dopa: A double-blind, controlled study. Neurology, 38(12), 1845. https://doi.org/10.1212/WNL.38.12.18453Aldhous, P. (2005). Drug rehabilitation: cold turkey, Vietnamese style. Nature, 433(7026), 568-9. https://doi.org/10.1038/433568a4Dias, C., Ahn, S., Ma, B., & Phillips, A.G. (2016). Behavioural and neurochemical assessment of heantos 4 on preclinical models of morphine-dependence. Journal of addiction research & therapy, 7(4), 292-303. https://doi.org/10.4172/2155-6105.1000292

Herbal Assist’s reformulation is based on availability of similar, cheaper, more accessible, or improved herbs available to TCM outside of Vietnam where Heantos originated. This mixture is designed to increase its effectiveness at improving sleep throughout the whole withdrawal process.

Herbal Assist is currently available through Ceiba directly. If you are interested in discussing this option please call +1 (888) 848-7972. I am currently doing simple survey-based observational research with my clients to learn more about its effectiveness.

Herbal Assist for Withdrawal

The protocol for doing at-home detox with Herbal Assist is to take up to 8-10 capsules as frequently as every 4-6 hours for as long as withdrawal symptoms persist. During this time most people report feeling drowsy. Other complimentary methods listed below may provide additional support both acutely and in the long term.

Herbal Assist for Post-Ibogaine Treatment

Herbal assist can serve as a natural, non-benzo/non-z-class sleep aid, as well as a way of reducing lingering withdrawal or physical PAWS. Because sleep can be a challenge for some people after ibogaine treatment, this can be an important resource. Others have notice that it has also helped to reduce cravings for opioids and alcohol post treatment.

High Dose Vitamin C

There is evidence that high doses of antioxidants, such as Vitamin C, can reduce the degradation of internal opioids increase endorphin levels. Also, Vitamin C helps to convert dopamine to norepinephrine, which is helpful in managing depression and mood swings.5Johnston, C. S., Barkyoumb, G. M., & Schumacher S.S. (2014). Vitamin C supplementation slightly improves physical activity levels and reduces cold incidence in men with marginal Vitamin C status: a randomized controlled trial. Nutrients, 6(7), 2572-2583. https://doi.org/10.3390/nu60725726Gariballa, C. (2014). Poor Vitamin C status is associated with increased depression symptoms following acute illness in older people. International journal of vitamin and nutrition research, 84(1-2), 12-7. https://doi.org/10.1024/0300-9831/a000188

There are some studies showing that supplementation with Vitamin C can lead to increases of mood, treating anxiety7Amr, M., El-Mogy, A., Shams, T., Vieira, K., & Lakhan, S.L. (2013). Efficacy of Vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. Nutrition journal, 12, 31. http://doi.org/10.1186/1475-2891-12-318de Olivera, I.J.L., de Souza, V.V., Motta, V., & Da-Silva, S. L. (2015). Effects of oral Vitamin C supplementation on anxiety in students: a double-blind, randomized, placebo-controlled trial. Pakistan journal of biological sciences , 18(1), 11-8. http://doi.org/10.1186/10.3923/pjbs.2015.11.189Mazloom, Z., Ekramzadeh, M., & Hejazi, N. (2013). Efficacy of supplementary vitamins C and E on anxiety, depression and stress in type 2 diabetic patients: a randomized, single-blind, placebo-controlled trial. Pakistan journal of biological science, 16(22), 1597-600. http://doi.org/10.3923/pjbs.2013.1597.1600 and depression.10Amr, M., El-Mogy, A., Shams, T., Vieira, K., & Lakhan, S.E. (2013). Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. Nutrition journal, 12, 31. http://doi.org/10.1186/1475-2891-12-31 11Brody S. (2002). High-dose ascorbic acid increases intercourse frequency and improves mood: a randomized controlled clinical trial. Biological psychiatry, 52(2), 371-4. http://doi.org/10.1016/s0006-3223(02)01329-x 12Sahraian, A., Ghanizadeh, A., & Kazemeini, F. (2015). Vitamin C as an adjuvant for treating major depressive disorder and suicidal behavior, a randomized placebo-controlled clinical trial. Trails, 16, 94. http://doi.org/10.1186/s13063-015-0609-1 13Gariballa, S. (2014). Poor vitamin C status is associated with increased depression symptoms following acute illness in older people. International journal of vitamin and nutrition Research, 84(1-2), 12-7. http://doi.org/10.1024/0300-9831/a000188 14Amr, M., El-Mogy, A., Shams, T., Vieira, K. & Lakhan, S.E. (2013). Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. Nutrition journal , 12, 31. http://doi.org/10.1186/1475-2891-12-31 This is especially the case when vitamin C deficiencies are present, but some studies show that amongst people who use drugs these can be present in up to 58% of cases. Uses of high doses of Vitamin C have even been shown to reduce opioid dependence and lead to reductions of opioid withdrawal.15Evangelou, A., Kalfakakou, V., Georgakas, P., Koutras, V., Vezyraki, P., lliopoulou, L., & Vadalouka, A. (2000). Ascorbic acid (Vitamin C) effects on withdrawal syndrome of heroin abusers. In vivo, 14(2), 363-6. https://pubmed.ncbi.nlm.nih.gov/10836211/16Talkhooncheh, M., Alaei, H.A., Ramshini, E., & Shahidani, S. (2014). The effect of Vitamin C on morphine self-administration in rats. Advanced biomedical research, 3, 178. http://doi.org/10.4103/2277-9175.139524 17Schauss, A.G. (2012). Attenuation of heroin withdrawal syndrome by the administration of high-dose Vitamin C. Journal of orthomolecular medicine, 27(4), 189-197. https://www.researchgate.net/publication/23683437518Schauss, A.G. (2012). Attenuation of heroin withdrawal syndrome by the administration of high-dose Vitamin C. Journal of orthomolecular medicine, 27(4), 189-197. https://www.researchgate.net/publication/23683437519Khanna, N.C.& Sharma, S.K. (1983). Megadoses of Vitamin C prevent the development of tolerance and physical dependence on morphine in mice. Life science, 33(suppl 1), 401-4. http://doi.org/10.1016/0024-3205(83)90527-120Johnston, P.A. & Chahl, L.A. (1992). Chronic treatment with ascorbic acid inhibits the morphine withdrawal response in guinea-pigs. Neuroscience letters, 135(1), 23-7. http://doi.org/10.1016/0304-3940(92)90127-s

Especially for higher doses recommended below, either the sodium ascorbate or calcium ascorbate forms of vitamin C provide better options than the common ascorbic acid because they are non-acidic and easier on the stomach.21Lee, J. K., Jung, S. H., Lee, S. E., Han, J. H., Jo, E., Park, H. S., Heo, K. S., Kim, D., Park, J. S., & Myung, C. S. (2018). Alleviation of ascorbic acid-induced gastric high acidity by calcium ascorbate in vitro and in vivo. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 22(1), 35–42. http://doi.org/10.4196/kjpp.2018.22.1.35

Vitamin C for Withdrawal

Research protocols using Vitamin C for detoxification use doses ranging from 30 to 85g a day, split up so that they are taken every 3 or 4 hours dissolved in water. If attempting to use Vitamin C for this purpose.

Vitamin C for Pre-Ibogaine treatment

Prior to ibogaine treatment Vitamin C may help with lowering opioid dependency or during medication switches. Taking into consideration the detoxification doses above, starting at 4 to 8g and taking every four hours or as needed may provide some relief. IV vitamin therapy is often used by clinics for as treatment preparation.

Vitamin C for Post-Ibogaine treatment

Vitamin C in lower dosages can help with general mood and well-being, while in gradually higher doses it may help to treat linger withdrawal or PAWS. Many people will notice beneficial effects of taking between 2 to 4g every day, or as needed.

Amino Acids &
Other Nutrient Supplements

Amino acids serve as building blocks for important proteins, as well as precursors to neurotransmitters such as dopamine, serotonin, GABA, and others. Normally we receive sufficient amino acids from our diet, but in some cases our diet is simply not able to produce a high enough quantity of amino acids necessary for neurotransmitter production. This can certainly be the case surrounding regular substance use, including during active dependence and post-acute detox.

While there are some clinics that offer IV amino and vitamin therapy, the following is a basic protocol that can be done at home for stimulating neurotransmitter production that some people have found is able to reduce some of the discomforts around treatment preparation, or post-treatment discomforts.

Sample Post-Detox Nutritional Protocol

While there is no one-sized fits all protocol, these are starting doses for people assuming a high level of nutritional need post detox that provide a sample detox protocol that can be adjusted. After a number of months, when beneficial effects start to stabilize the dosages of some of the dosages mentioned below should be lowered.

DLPA
4000mg/day down to 1500mg/day in the morning only

5-HTP
200mg twice a day, morning and afternoon

SAM-e
1600mg/day

GABA supplements
Kava, magnolia bark extracts, or valerian (see below)

Vitamin C (sodium ascorbate or calcium ascorbate version)
2-4g/day or as needed

Vitamin B12
1000µg/day

Magnesium
1000mg/day

Probiotics
Foods and supplements (see below)

Dopamine Precursors

DLPA

DLPA is a mixture of D-phenylalanine (DPA) and L-phenylalanine (LPA). LPA is an organic precursor of tyrosine, which our bodies later convert into dopamine. DPA is synthetic and has been shown to have some benefits including positive effects on mood and to increase levels of internal opioids. Theoretically, the mixture of the two provides the benefits of both while reducing the side effects of taking either.22Camacho, F., & Mazuecos, J. (2002). Oral and topical L-phenylalanine, clobetasol propionate, and UVA/sunlight–a new study for the treatment of vitiligo. Journal of drugs in dermatology, 1(2), 127-31. https://pubmed.ncbi.nlm.nih.gov/12847735/ 23Zametkin, A.J., Karoum, F., & Rapoport, J.L. (1987). Treatment of hyperactive children with D-phenylalanine. American journal of psychiatry, 144(6), 792-4. http://doi.org/10.1176/ajp.144.6.792 24Fischer, E., Heller, B., Nachon, M., & Spatz, H. (1975). Therapy of depression by phenylalanine. Preliminary note. Arzneimittelforschung, 25(1), 132. https://pubmed.ncbi.nlm.nih.gov/1173765/ 25Beckmann, H., Strauss, M.A., Ludolph, E. (1977). Dl-phenylalanine in depressed patients: an open study. Journal of neural transmission, 41(2-3), 123-34. http://doi.org/10.1007/BF01670277 26Beckmann, H., Athen, D., Olteanu, M., & Zimmer, R. (1979). DL-phenylalanine versus imipramine: a double-blind controlled study.Arch psychiatr nervenkr, 227(1), 49-58. http://doi.org/10.1007/BF00585677 27Wood, D.R., Reimherr, F.W., & Wender, P.H. (1985).Treatment of attention deficit disorder with DL-phenylalanine. Psychiatry research, 16(1), 21-6. http://doi.org/10.1016/0165-1781(85)90024-1

There is evidence that either LPA or the mixture of the two has been good as a treatment or treatment adjunct for depression.28Birkmayer, W., Riederer, P., Linauer, W., & Knoll, J. (1984). L-deprenyl plus L-phenylalanine in the treatment of depression. Journal of neural transmission, 59(1), 81-7. http://doi.org/10.1007/BF01249880 29Beckmann, H., Athen, D., Olteanu, M., & Zimmer, R. (1970). DL-phenylalanine versus imipramine: a double-blind controlled study. Arch psychiatr nervenkr, 227(1), 49-58. http://doi.org/10.1007/BF00585677 30Beckmann, H., Strauss, M.A., & Ludolph, E. (1977). Dl-phenylalanine in depressed patients: an open study. Journal of neural transmission, 41(2-3), 123-34. http://doi.org/10.1007/BF01670277 31Fischer, E., Heller, B., Nachon, M., & Spatz, H. (1975). Therapy of depression by phenylalanine. Preliminary note. Arzneimittelforschung, 25(1), 132. https://pubmed.ncbi.nlm.nih.gov/1173765/

There is some evidence that DPA alone and with other amino acids can help to improve mood, reduce stress, and lower psychiatric symptoms of people going through opioid or alcohol treatment.32Ehrenpreis S. (1985). Analgesic properties of enkephalinase inhibitors: animal and human studies. Progress in clinical biological research, 192, 363-70. https://pubmed.ncbi.nlm.nih.gov/2934746/ 33Beckmann, H., Athen, D., Olteanu, M., & Zimmer, R. (1970). DL-phenylalanine versus imipramine: a double-blind controlled study. Arch psychiatr nervenkr, 227(1), 49-58. http://doi.org/10.3727/036012982816952099 34Beckmann, H., Strauss, M.A., & Ludolph, E. (1977). Dl-phenylalanine in depressed patients: an open study. Journal of neural transmission, 41(2-3), 123-34. https://pubmed.ncbi.nlm.nih.gov/22397264/ 35Fischer, E., Heller, B., Nachon, M., & Spatz, H. (1975). Therapy of depression by phenylalanine. Preliminary note. Arzneimittelforschung, 25(1), 132. http://doi.org/10.1016/0741-8329(87)90084-x

There are some case studies indicating that larger doses of DLPA can help to reduce chronic pain.36Russell, A.L., & McCarty, M.F. (2000). DL-phenylalanine markedly potentiates opiate analgesia – an example of nutrient/pharmaceutical up-regulation of the endogenous analgesia system. Medical hypotheses, 55(4), 283-8. http://doi.org/10.1054/mehy.1999.1031

Serotonin Precursors

5-HTP

5-Hydroxytryptophan (5-HTP) is a serotonin precursor that is extracted from the seeds of Griffonia simplicifolia. Some studies have shown that supplementing with 5-HTP is as effective as some prescription anti-depressants without the effect of creating dependency and some of the other negative side effects of those medications.37Shaw, K., Turner, J., & Del Mar, C. (2002). Tryptophan and 5-hydroxytryptophan for depression. Cochrane database of systmatic reviews, (1), CD003198. http://doi.org/10.1002/14651858.CD003198 38Jangid, P., Malik, P., Singh, P., Sharma, M., & Gulia, A.K.(2013). Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode.
Asian Journal of psychiatry, 6(1), 29-34. http://doi.org/10.1016/j.ajp.2012.05.011

For others who are taking SSRI anti-depressants, there is some evidence that co-administration of 5-HTP increases serotonin levels beyond what is produced by either individually.39Perry, K.W., & Fuller, R.W. (1993). Extracellular 5-hydroxytryptamine concentration in rat hypothalamus after administration of fluoxetine plus L-5-hydroxytryptophan. Journal of pharmacy and pharmacology, 45(8), 759-61. http://doi.org/10.1111/j.2042-7158.1993.tb07105.x40Lowe, S.L., Yeo, K.P., Teng, L., Soon, D.K., Pan, A., Wise, S.D., & Peck, R.W. (2006). L-5-Hydroxytryptophan augments the neuroendocrine response to a SSRI.Psychoneuroendocrinology, 31(4), 473-84. http://doi.org/10.1016/j.psyneuen.2005.11.005 41Jacobsen, J.P.R., Krystal, A.D., Krishnan, K.R.R., & Caron, M.G. (2016). Adjunctive 5-hydroxytryptophan slow-Release for treatment-resistant depression: clinical and preclinical rationale. Trends in pharmacological sciences, 37(11), 933-944. http://doi.org/10.1016/j.tips.2016.09.00142Lowe, S.L., Yeo, K.P., Teng, L., Soon, D.K., Pan, A., Wise, S.D., & Peck, R.W. (2006). L-5-Hydroxytryptophan augments the neuroendocrine response to a SSRI. Psychoneuroendocrinology, 31(4), 473-84. http://doi.org/10.1016/j.psyneuen.2005.11.005

Other studies have shown that 5-HTP can have some beneficial effects on opioid withdrawal symptoms43Akaoka, H., & Aston-Jones, G. (1993). Indirect serotonergic agonists attenuate neuronal opiate withdrawal. Neuroscience, 54(3), 561-565. https://doi.org/10.1016/0306-4522(93)90227-744Dais, J., Khosia, A., & Doulatram, G. (2015). The successful treatment of opioid withdrawal-induced refractory muscle spasms with 5-HTP in a patient intolerant to clonidine. Pain physician, 18(3), E417-20. https://pubmed.ncbi.nlm.nih.gov/26000689/ and cravings.45Harris, G.C., & Aston-Jones, G. (2001). Augmented accumbal serotonin levels decrease the preference for a morphine associated environment during withdrawal. Neuropsychopharmacology, 24(1), 75-85. https://doi.org/10.1016/S0893-133X(00)00184-6 The mechanism of this may be by reducing morphine tolerance.46Contreras, E., Tamayo, L., Quijada, L., & Silva, E. (1973). Decrease of tolerance development to morphine by 5-hydroxytryptophan and some related drugs. European journal of pharmacology, 22(3), 339-43. https://doi.org/10.1016/0014-2999(73)90035-6

SAM-e

SAM-e (S-Adenosyl-L-methionine) is a serotonin precursor that is produced endogenously in the body. Supplementing with SAM-e is one of the most researched alternative treatments for depression, showing that is well tolerated and as effective as prescription anti-depressants,47Mischoulon, D., & Fava, M. (2002). Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. The American journal of clinical nutrition, 76(5), 1158S-61S. http://doi.org/10.1093/ajcn/76/5.1158S 48Papakostas, G.I.(2009). Evidence for S-adenosyl-L-methionine (SAM-e) for the treatment of major depressive disorder. Journal of Clinical psychiatry, 70 Suppl 5, 18-22. http://doi.org/10.4088/JCP.8157su1c.04 49De Berardis, D., Orsolini, L., Serroni, N., Girinelli, G., Iasevoli, F., Tomasetti, C., de Bartolomeis, A., Mazza, M., Valchera, A., Fornaro, M., Perna, G., Piersanti, M., Di Nicola, M., Cavuto, M., Martinotti, G., & Di Giannantonio, M. (2016). A comprehensive review on the efficacy of S-Adenosyl-L-methionine in Major Depressive Disorder. CNS & neurological disorders-drug targets, 15(1), 35-44. http://doi.org/10.2174/187152731466615082110382550Galizia, I., Oldani, L., Macritchie, K., Amari, E., Dougall, D., Jones, T. N., Lam, R. W., Massei, G. J., Yatham, L. N., & Young, A. H. (2016). S-adenosyl methionine (SAMe) for depression in adults. The Cochrane database of systematic reviews, 10(10), CD011286. http://doi.org/10.1002/14651858.CD011286.pub2 including for treatment resistant depression in 30-60% of cases.51Papakostas, G.I., Mischoulon, D., Shyu, I., Alpert, J.E., & Fava, M. (2010) S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. American journal of psychiatry, 167(8), 942-8. http://doi.org/10.1176/appi.ajp.2009.09081198 52 Bambling, M., Parham,S. C.,Coulson,S.& Vitetta,L.(2015).S-adenosylmethionine (SAMe) and Magnesium Orotate as adjunctives to SSRIs in sub-optimal treatment response of depression in adults: A pilot study. Advances in integrative medicine, 2(1), 56-62. https://doi.org/10.1016/j.aimed.2015.04.00353De Berardis, D., Marini, S., Serroni, N., Rapini, G., Iasevoli, F., Valchera, A., Signorelli, M., Aguglia, E., Perna, G., Salone, A., Di Iorio, G., Martinotti, G., & Di Giannantonio, M. (2013). S-Adenosyl-L-Methionine augmentation in patients with stage II treatment-resistant major depressive disorder: an open label, fixed dose, single-blind study.The scientific world journal, 204649. http://doi.org/10.1155/2013/20464954Alpert, J.E., Papakostas, G., Mischoulon, D., Worthington, J.J. 3rd, Petersen, T., Mahal, Y., Burns, A., Bottiglieri, T., Nierenberg, A.A., & Fava, M. (2004). S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine. Journal of clinical psychopharmacology, 24(6), 661-4. http://doi.org/10.1097/01.jcp.0000145339.45794.cd Some studies highlighted that while providing these benfits SAM-e increased cognition and lowered sexual dysfunction caused by antidepressants.55Levkovitz, Y., Alpert, J.E., Brintz, C.E., Mischoulon, D., & Papakostas, G.I. (2012). Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder. European psychiatry, 27(7), 518-21. http://doi.org/10.1016/j.eurpsy.2011.03.00656Dording, C.M., Mischoulon, D., Shyu, I., Alpert, J.E., & Papakostas, G.I. (2012).SAMe and sexual functioning. European psychiatry, 27(6), 451-4. http://doi.org/10.1016/j.eurpsy.2011.01.003

While 5-HTP can be combined with other antidepressants, there are health advisory warnings against combining SAM-e with prescription antidepressant medications.57SAMe. Mayo Clinic. https://www.mayoclinic.org/drugs-supplements-same/art-20364924

GABA & GABA Precursors

GABA is a neurotransmitter, like serotonin and dopamine, that has been linked to depression58Byun, J.I., Shin, Y.Y., Chung, S.E., & Shin, W.C. (2018). Safety and efficacy of Gamma-Aminobutyric Acid from fermented rice germ in patients with insomnia symptoms: a randomized, double-blind trial. Journal of clinical neurology, 14(3), 291-295. http://doi.org/10.3988/jcn.2018.14.3.291 59Luscher, B., Shen, Q., & Sahir, N. (2011). The GABAergic deficit hypothesis of major depressive disorder. Molecular psychiatry, 16(4), 383–406. http://doi.org/10.1038/mp.2010.12060Yang, L., Xu, T., Zhang, K., Wei, Z., Li, X., Huang, M., Rose, G.M., & Cai, X.(2016). The essential role of hippocampal alpha6 subunit-containing GABAA receptors in maternal separation stress-induced adolescent depressive behaviors. Behavioural brain research, 313, 135-143. http://doi.org/10.1016/j.bbr.2016.07.002 and anxiety,61Möhler, H. (2009). Role of GABAA receptors in cognition. Biochemical society transactions, 37(Pt 6), 1328-33. http://doi.org/10.1042/BST037132862Luscher, B., Shen, Q., & Sahir, N. (2011). The GABAergic deficit hypothesis of major depressive disorder. Molecular psychiatry, 16(4), 383–406. http://doi.org/10.1038/mp.2010.120 63Anxiety neurotransmitters. https://thebrain.mcgill.ca/flash/d/d_04/d_04_m/d_04_m_peu/d_04_m_peu.html as well as to substance addiction.64Filip, M., & Frankowska, M. (2008). GABA(B) receptors in drug addiction. Pharmacological reports, 60(6), 755-70. https://pubmed.ncbi.nlm.nih.gov/19211967/ GABA receptors are the target for drugs like benzodiazepines that are generally described in these contexts, as well as for z-class drugs that are prescribed for sleep.

Increased levels of GABA may help to stimulate neurogenesis, the growth of new brain cells65Luscher, B., Shen, Q., & Sahir, N. (2011). The GABAergic deficit hypothesis of major depressive disorder. Molecular psychiatry, 16(4), 383–406. http://doi.org/10.1038/mp.2010.120 66Krystal, J.H., Sanacora, G., Blumberg, H., Anand, A., Charney, D.S., Marek, G., Epperson, C.N., Goddard, A., & Mason, G.F. (2002). Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Molecular psychiatry, 7 Suppl 1, S71-80. http://doi.org/10.1038/sj.mp.4001021 which has been linked to improved mood.

There is also evidence that increasing GABA can play a role in easing substance withdrawal.67Filip, M., & Frankowska, M.(2008). GABA(B) receptors in drug addiction. Pharmacological reports, 60(6), 755-70. https://pubmed.ncbi.nlm.nih.gov/19211967/ 68Filip, M., Frankowska, M., Sadakierska-Chudy, A., Suder, A., Szumiec, L., Mierzejewski, P., Bienkowski, P., Przegali?ski, E., & Cryan, J.F. (2015). GABAB receptors as a therapeutic strategy in substance use disorders: focus on positive allosteric modulators. Neuropharmacology, 88, 36-47. 10.1016/j.neuropharm.2014.06.01669Phillips, T.J., & Reed, C.(2014). Targeting GABAB receptors for anti-abuse drug discovery. Expert Opinion on drug discovery, 9(11), 1307-1. http://doi.org/10.1517/17460441.2014.956076 [/mfn

GABA is available as an over-the-counter supplement, however its utility in this form is contested. One clinical trial has linked GABA supplementation over 4 weeks with improvements in quality of sleep and reducing the time it takes to fall asleep,69Byun, J.I., Shin, Y.Y., Chung, S.E., & Shin, W.C. (2018). Safety and efficacy of Gamma-Aminobutyric Acid from fermented rice germ in patients with insomnia symptoms: a randomized, double-blind trial. Journal of clinical neurology, 14(3), 291-295. http://doi.org/10.3988/jcn.2018.14.3.291
however this study was conducted by a producer and the results have not been able to be mimicked. There is no conflicting evidence that GABA supplements are able to cross the blood brain barrier, and if they are its possible that they leave the blood too quickly to be able to have a beneficial effect.

There are, however, other natural substances that can increase levels of GABA and contain some of the benefits in terms of relaxation, reducing anxiety and depression, and promoting sleep.

Kava

Kava has other effects, but one of its six psychoactive components, kavain, stimulates GABA-A receptors.70Chua, H.C., Christensen, E.T., Hoestgaard-Jensen, K., Hartiadi, L.Y., Ramzan, I., Jensen, A.A., Absalom, N.L., & Chebib, M. (2016). Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional dharacteristics and molecular mechanism. PLoS one, 11(6), e0157700. http://doi.org/10.1371/journal.pone.015770071Jussofie, A., Schmiz, A., & Hiemke, C. (1994). Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of rat brain. Psychopharmacology (Berl), 116(4), 469-74. http://doi.org/10.1007/BF02247480. There are studies that show kava has improved symptoms of anxiety,72Sarris, J., Kavanagh, D.J., Byrne, G., Bone, K.M., Adams, J., & Deed, G. (2009). The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology (Berl), 205(3), 399-407. http://doi.org/10.1007/s00213-009-1549-973Sarris, J., Stough, C., Bousman, C.A., Wahid, Z.T., Murray, G., Teschke, R., Savage, K.M., Dowell, A., Ng, C., & Schweitzer, I. (2013). Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. Journal of clinical psychopharmacology, 33(5), 643-8. http://doi.org/10.1097/JCP.0b013e318291be67 74Sarris, J., Stough, C., Teschke, R., Wahid, Z.T., Bousman, C.A., Murray, G., Savage, K.M., Mouatt, P., Ng, C., & Schweitzer, I. (2013). Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects. Phytotherapy research, 27(11), 1723-8. http://doi.org/10.1002/ptr.4916 stress and insomnia,75Wheatley, D. (2001). Stress-induced insomnia treated with kava and valerian: singly and in combination.
Human psychopharmacology, 16(4), 353-356. http://doi.org/10.1002/hup.299
76Lehrl, S. (2004).Clinical efficacy of kava extract WS 1490 in sleep disturbances associated with anxiety disorders. Results of a multicenter, randomized, placebo-controlled, double-blind clinical trial. Journal of affective disorders, 78(2), 101-10. http://doi.org/10.1016/s0165-0327(02)00238-0 depression, restlessness and tension, and improved sleep quality and cognition77Gastpar, M., & Klimm, H.D.(2003).Treatment of anxiety, tension and restlessness states with Kava special extract WS 1490 in general practice: a randomized placebo-controlled double-blind multicenter trial. Phytomedicine, 10(8), 631-9. http://doi.org/10.1078/0944-7113-00369 78Thompson, R., Ruch, W., & Hasenöhrl, R.U. (2004).Enhanced cognitive performance and cheerful mood by standardized extracts of Piper methysticum (Kava-kava). Human psychopharmacology, 19(4), 243-50. http://doi.org/10.1002/hup.581 79Volz, H.P., & Kieser, M.(1997). Kava-kava extract WS 1490 versus placebo in anxiety disorders-a randomized placebo-controlled 25-week outpatient trial. Pharmacopsychiatry, 30(1), 1-5. http://doi.org/10.1055/s-2007-979474 and studies report no evidence of addiction or withdrawal symptoms that are common with other anxiety medications.80Scherer, J. (1998). Kava-kava extract in anxiety disorders: an outpatient observational study. Advances in therapy, 15(4), 261-9. https://pubmed.ncbi.nlm.nih.gov/10186945/ 81Sarris, J., Stough, C., Teschke, R., Wahid, Z.T., Bousman, C.A., Murray, G., Savage, K.M., Mouatt, P., Ng, C., & Schweitzer, I. (2013). Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver research, 27(11), 1723-8. http://doi.org/10.1002/ptr.491682Weaver M. F. (2015). Prescription Sedative Misuse and Abuse. The Yale journal of biology and medicine, 88(3), 247–256. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553644/

Because kava has effects on the liver you should not take it if you have liver issues if you are taking any prescription drugs. If you take kava for longer than one to two months you will benefit from regular liver function tests.

Daily dosage of kavalactones should not exceded 250mg. This needs to be taken into consideration when considering kava products. Kava root extracts range between 30-70%. Therefore a 100mg capsule of 30% extract would be 30mg of kavalactones.

Magnolia Bark

Magnolia bark extracts, including honokiol and magnolol modulate GABA-A receptors and alleviate anxiety, depression, and seizures by promoting relaxation.83Alexeev, M.,Grosenbaugh,D. K., Mott,D. D., & Fisher, J. L. (2012). The natural products magnolol and honokiol are positive allosteric modulators of both synaptic and extra synaptic GABAA receptors. Neuropharmacology, 62(8), 2507-2514. https://doi.org/10.1016/j.neuropharm.2012.03.00284Chen, C.R., Tan, R., Qu, W.M., Wu, Z., Wang, Y., Urade, Y., & Huang, Z.L. (2011).Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/benzodiazepine receptor complex in mice. British journal of pharmacology, 164(5), 1534-46.http://doi.org/10.1111/j.1476-5381.2011.01456.x85Xu, Q., Yi, L.T., Pan, Y., Wang, X., Li, Y.C., Li, J.M., Wang, C.P., & Kong, L.D.(2008). Antidepressant-like effects of the mixture of honokiol and magnolol from the barks of Magnolia officinalis in stressed rodents. Progress in neuropsychopharmacology & biological psychiatry, 32(3), 715-25. http://doi.org/10.1016/j.pnpbp.2007.11.02086Kuribara, H., Kishi, E., Hattori, N., Okada, M., & Maruyama, Y. (2000).The anxiolytic effect of two oriental herbal drugs in Japan attributed to honokiol from magnolia bark. Journal of pharmacy and pharmacology 52(11),1425-9. http://doi.org/10.1211/0022357001777432

Honokiol can have antithrombotic effects, reducing body’s ability form blood clots, and should not be taken if you have a blood clotting condition.87Li, Q.X., & Dowhan, W. (1990). Studies on the mechanism of formation of the pyruvate prosthetic group of phosphatidylserine decarboxylase from Escherichia coli. Journal of biological chemistry, 265(7), 4111-5. https://pubmed.ncbi.nlm.nih.gov/2406271/

Again, there are no cases of dependence or withdrawal that have been reported.

Dosages are usually suggested around 250mg one to two times per day.

Valerian root

Valerian root is a traditional herbal medicine used to promote relaxation and reduce stress.88Houghton, P.J. (1999). The scientific basis for the reputed activity of Valerian. Journal of pharmacy and pharmacology, 51(5), 505-12. http://doi.org/10.1211/0022357991772772

It has been shown in over 20 human trials to reliably improve the time it takes to fall asleep and sleep quality in people with insomnia, as well as symptoms of OCD and restlessness.89Taavoni, S., Ekbatani, N., Kashaniyan, M., & Haghani, H.(2011). Effect of valerian on sleep quality in postmenopausal women: a randomized placebo-controlled clinical trial. Menopause, 18(9), 951-5. http://doi.org/10.1097/gme.0b013e31820e9acf 90Pakseresht, S., Boostani, H., & Sayyah, M. (2011). Extract of valerian root (Valeriana officinalis L.) vs. placebo in treatment of obsessive-compulsive disorder: a randomized double-blind study. Journal of complementary and integrative medicine, 8(1). http://doi.org/10.2202/1553-3840.1465 91Bent, S., Padula, A., Moore, D., Patterson, M., & Mehling, W. (2006). Valerian for sleep: a systematic review and meta-analysis. The American journal medicine, 119(12), 1005-12. http://doi.org/10.1016/j.amjmed.2006.02.026 92Cuellar, N.G., & Ratcliffe, S.J. (2009). Does valerian improve sleepiness and symptom severity in people with restless legs syndrome?. Alternative therapies in health and medicine, 15(2), 22-8. https://pubmed.ncbi.nlm.nih.gov/19284179/

While Valerian root can be purchased as a supplement, there may be benefits to taking its primary extract, valerinic acid, which is shown to modulate GABA-A receptors93Benke,D., Barberis, A., Kopp, S., Altmann, K., Schubiger, M., Vogt,K. E., Rudolph, U., & Möhler, H. (2009). GABAA receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts. Neuropharmacology, 56(1), 174-181. https://doi.org/10.1016/j.neuropharm.2008.06.013 while valerian plants without valerinic acid do not.94Wasowski, C., Marder, M., Viola, H., Medina, J.H., & Paladini, A.C. (2002). Isolation and identification of 6-methylapigenin, a competitive ligand for the brain GABA(A) receptors, from Valeriana wallichii. Planta medica, 68(10), 934-6. http://doi.org/10.1055/s-2002-34936 95Santos, M.S., Ferreira, F., Cunha, A.P., Carvalho, A.P., Ribeiro, C.F., & Macedo, T. (1994). Synaptosomal GABA release as influenced by valerian root extract–involvement of the GABA carrier. Archives internationales de pharmacodynamie et de therapie, 327(2), 220-31. https://pubmed.ncbi.nlm.nih.gov/7979830/

Dosages that have been shown to help with sleep range from 300mg to 1000mg.

Additional Nutritional Supplements

Vitamin B12 (folic acid)

Some research shows that deficiencies of Vitamin B12 can impair the production of endogenous SAM-e and lead to lower levels of serotonin and noradrenaline. Supplementing with Vitamin B12 may have a positive impact on depression,96De Berardis, D., Orsolini, L., Serroni, N., Girinelli, G., Iasevoli, F., Tomasetti, C., de Bartolomeis, A., Mazza, M., Valchera, A., Fornaro, M., Perna, G., Piersanti, M., Di Nicola, M., Cavuto, M., Martinotti, G., & Di Giannantonio, M.(2016). A comprehensive review on the efficacy of S-Adenosyl-L-methionine in Major Depressive Disorder. CNS and neurological disorders- drug targets, 15(1), 35-44. http://doi.org/10.2174/1871527314666150821103825 while others show further benefits when taken in with SAM-e.97Djokic, G., Korcok, D., Djordjevic, V., Agic, A., Rankovic, A., & Djukic, D. (2017). The effects of S-adenosyl-L-methionine-vitamin B complex on mild and moderate depressive symptoms. Hippokratia, 21(3), 140–143. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247995/

There is some evidence, perhaps supported by this effect, that Vitamin B12 alone can help to reduce morphine tolerance and have an effect on withdrawal symptoms.98Ghazanfari, S., Imenshahidi, M., Etemad, L., Moshiri, M., & Hosseinzadeh, H.(2014). Effect of cyanocobalamin (Vitamin B12) in the induction and expression of morphine tolerance and dependence in mice. Drug research (Stuttg), 64(3), 113-7. http://doi.org/10.1055/s-0033-1355364

Magnesium

Magnesium promotes neurotransmitter production and regulation99Wallasch, T. M. (2009). Migraine and tension headache. Complementary and alternative methods. MMW fortschritte medizin, 151(43), 42-3. https://www.racgp.org.au/afpbackissues/2005/200508/200508woolhouse.pdf and has a number of different health benefits. It has also been shown to directly reduce opioid dependence and withdrawal symptoms by a number of different mechanisms.100Nechifor, M.(n.d.). Magnesium in drug abuse and addiction. Magnesium in the Central Nervous System, 333–344. https://www.ncbi.nlm.nih.gov/books/NBK507260/#101Naderi-Heiden, A., Frey, R., Presslich, O., Frottier, P., Willinger, U., Blasbichler, T., Smetana, R., Schmid, D., & Kasper, S. (2005). Effect of intravenous magnesium sulphate in reducing irritability and restlessness in pure and polysubstance opiate detoxification. Psychiatry research, 135(1),53-63. http://doi.org/10.1016/j.psychres.2004.07.012102Nechifor, M., Chelarescu, D., & Miftode, M. (2004). Magnesium influence on morphine-induced pharmacodependence in rats. Magnesium research, 17(1), 7-13. https://pubmed.ncbi.nlm.nih.gov/15083563/103Rotter, I., Kosik-Bogacka, D., Dolegowska, B., Safranow, K., Karakiewicz, B., & Laszczynska, M.(2015). Relationship between serum magnesium concentration and metabolic and hormonal disorders in middle-aged and older men. Magnesium research, 28(3), 99-107. http://doi.org/10.1684/mrh.2015.0391

There is also evidence that low levels of magnesium are correlated with depression104Serefko, A., Szopa, A., Wlaz, P., & Nowak, G., Radziwon-Zaleska, M., Skalski, M., & Poleszak, E. (2013). Magnesium in depression. Pharmacological reports, 65(3), 547-54. http://doi.org/10.1016/s1734-1140(13)71032-6105Tarleton, E.K., & Littenberg, B. (2015). Magnesium intake and depression in adults. Journal of American board of family medicine, 28(2), 249-56. http://doi.org/10.3122/jabfm.2015.02.140176 and that supplementing with magnesium can reduce symptoms of depression.106Eby, G.A., & Eby, K.L. (2006). Rapid recovery from major depression using magnesium treatment. Medical hypotheses, 67(2), 362-70. http://doi.org/10.1016/j.mehy.2006.01.047 107Barragán-Rodríguez, L., Rodríguez-Morán, M., & Guerrero-Romero, F. (2008). Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial. Magnesium research, 21(4), 218-23. https://pubmed.ncbi.nlm.nih.gov/19271419/ 108Barragán-Rodríguez, L., Rodríguez-Morán, M., & Guerrero-Romero, F. (2008). Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial. Magnesium research, 21(4), 218-23. https://pubmed.ncbi.nlm.nih.gov/19271419/

Probiotics

The human gut is home to a vast array of bacteria that play a central role in many of the body’s processes.

Most direct in relation to reducing substance dependence is one study has found that probiotics can reduce morphine tolerance in mice, implicating gut flora in the modulation of withdrawal.109Zhang, L., Meng, J., Ban, Y., Jalodia, R., Chupikova, I., Fernandez, I., Brito, N., Sharma, U., Abreu, M.T., Ramakrishnan, S., & Roy, S. (2019). Morphine tolerance is attenuated in germfree mice and reversed by probiotics, implicating the role of gut microbiome. Proceedings of the national academy of sciences the USA, 116(27), 13523-13532. https://www.pnas.org/content/116/27/13523.short Additionally, opiates and other drugs can have a major impact on gut health in general, and are associated with a number of gut disorders.110Grunkemeier, D. M., Cassara, J. E., Dalton, C. B., & Drossman, D. A. (2007). The narcotic bowel syndrome: clinical features, pathophysiology, and management. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 5(10), 1126–1122. http://doi.org/10.1016/j.cgh.2007.06.013111Farmer, A. D., Ferdinand, E., & Aziz, Q. (2013). Opioids and the gastrointestinal tract – a case of narcotic bowel syndrome and literature review. Journal of neurogastroenterology and motility, 19(1), 94–98. http://doi.org/10.5056/jnm.2013.19.1.94

Probiotics have been shown to repair drug inducted gastro-intestinal damage.112Huang, R., Wang, K., & Hu, J. (2016). Effect of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials. Nutrients, 8(8), 483. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997396/ 113Witsell, D.L., Garrett, C.G., Yarbrough, W.G., Dorrestein, S.P., Drake, A.F., & Weissler, M.C. (1995). Effect of Lactobacillus acidophilus on antibiotic-associated gastrointestinal morbidity: a prospective randomized trial. Journal of otolaryngology, 24(4), 230-3. https://pubmed.ncbi.nlm.nih.gov/8551535/ 114Endo, H., Higurashi, T., Hosono, K., Sakai, E., Sekino, Y., Iida, H., Sakamoto, Y., Koide, T., Takahashi, H., Yoneda, M., Tokoro, C., Inamori, M., Abe, Y., & Nakajima, A. (2011). Efficacy of Lactobacillus casei treatment on small bowel injury in chronic low-dose aspirin users: a pilot randomized controlled study. Journal of gastroenterology, 46(7), 894-905. http://doi.org/10.1007/s00535-011-0410-1115Korpela, K., Salonen, A., Virta, L. J., Kumpu, M., Kekkonen, R. A., & de Vos, W. M. (2016). Lactobacillus rhamnosus GG intake modifies preschool children’s intestinal microbiota, alleviates Penicillin-associated changes, and reduces antibiotic use. PloS one, 11(4), e0154012. http://doi.org/10.1371/journal.pone.0154012

Probiotics also assist with the production of and absorption of nutrients116Moslehi-Jenabian, S., Pedersen, L. L., & Jespersen, L. (2010). Beneficial effects of probiotic and food borne yeasts on human health. Nutrients, 2(4), 449–473. http://doi.org/10.3390/nu2040449 including some of the ones listed above, Vitamin B12117Taranto,.M.P., Vera, J.L., Hugenholtz, J., De Valdez, G.F., & Sesma, F. (2003). Lactobacillus reuteri CRL1098 produces cobalamin. Journal of bacteriology, 185(18), 5643-7. http://doi.org/10.1128/jb.185.18.5643-5647.2003 and magnesium.118Moslehi-Jenabian, S., Pedersen, L.L., & Jespersen, L. (2010). Beneficial effects of probiotic and food borne yeasts on human health. Nutrients, 2(4), 449–473. http://doi.org/10.3390/nu2040449 118119Antai, S.P., & Nkwelang, G. (1999). Reduction of some toxicants in Icacina mannii by fermentation with Saccharomyces cerevisiae. Plant foods for human nutrition, 53(2), 103-11. http://doi.org/10.1023/a:1008060029175

On top of many other functions, 80-90% of all neurotransmitter that we produce come from our gut.120Mittal, R., Debs, L. H., Patel, A. P., Nguyen, D., Patel, K., O’Connor, G., Grati, M., Mittal, J., Yan, D., Eshraghi, A. A., Deo, S. K., Daunert, S., & Liu, X. Z. (2017). Neurotransmitters: the critical modulators regulating gut-brain axis. Journal of cellular physiology, 232(9), 2359–2372. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772764/ 121Strandwitz, P. (2018). Neurotransmitter modulation by the gut microbiota. Brain research, 1693(Pt B), 128–133. http://doi.org/10.1016/j.brainres.2018.03.015 Taking probiotics can help to increase neurotransmitters like serotonin, dopamine and GABA,122Huang, R., Wang, K., & Hu, J. (2016). Effect of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials. Nutrients, 8(8), 483. http://doi.org/10.3390/nu8080483 and there is evidence that they can have a positive effect on depression,123Huang, R., Wang, K., & Hu, J. (2016). Effect of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials. Nutrients, 8(8), 483. http://doi.org/10.3390/nu8080483124Steenbergen, L., Sellaro, R., van Hemert, S., Bosch, J.A., & Colzato, L.S.(2015). A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain, behavior, and immunity, 48, 258-64. http://doi.org/10.1016/j.bbi.2015.04.003125Huang, R., Wang, K., & Hu, J. (2016). Effect of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials. Nutrients, 8(8), 483. http://doi.org/10.3390/nu8080483 anxiety and stress,126Messaoudi, M., Violle, N., Bisson, J.F., Desor, D., Javelot, H., & Rougeot, C. (2011). Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut microbes, 2(4), 256-61. https://doi.org/10.4161/gmic.2.4.16108127Takada, M., Nishida, K., Kataoka-Kato, A., Gondo, Y., Ishikawa, H., Suda, K, Kawai, M., Hoshi, R., Watanabe, O., Igarashi, T., Kuwano, Y., Miyazaki, K., & Rokutan, K. (2016). Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models. Neurogastroenterology & motility, 28(7), 1027-36. http://doi.org/10.1111/nmo.12804128Langkamp-Henken, B., Rowe, C.C., Ford, A.L., Christman, M.C., Nieves, C. Jr, Khouri, L., Specht, G.J., Girard, S.A., Spaiser, S.J., & Dahl, W.J. (2015). Bifidobacterium bifidum R0071 results in a greater proportion of healthy days and a lower percentage of academically stressed students reporting a day of cold/flu: a randomised, double-blind, placebo-controlled study. British journal of nutrition, 113(3), 426-34. http://doi.org/10.1017/S0007114514003997129Culpepper, T., Christman, M.C., Nieves, C. Jr, Specht, G.J., Rowe, C.C., Spaiser, S.J., Ford, A.L., Dahl, W.J., Girard, S.A., & Langkamp-Henken, B. (2016). Bifidobacterium bifidum R0071 decreases stress-associated diarrhoea-related symptoms and self-reported stress: a secondary analysis of a randomised trial. Beneficial microbes, 7(3), 327-36. http://doi.org/10.3920/BM2015.0156 and even sleep.130Yamamura, S., Morishima, H., Kumano-go, T., Suganuma, N., Matsumoto, H., Adachi, H., Sigedo, Y., Mikami, A., Kai, T., Masuyama, A., Takano, T., Sugita, Y., & Takeda, M. (2009). The effect of Lactobacillus helveticus fermented milk on sleep and health perception in elderly subjects. European Journal of clinical nutrition, 63(1), 100-5. http://doi.org/10.1038/sj.ejcn.1602898 131Nakakita, Y., Tsuchimoto, N., Takata, Y., & Nakamura, T. (2016). Effect of dietary heat-killed Lactobacillus brevis SBC8803 (SBL88™) on sleep: a non-randomised, double blind, placebo-controlled, and crossover pilot study. Benefical microbes,7(4),501-9. http://doi.org/10.3920/BM2015.0118

Probably the best way to take probiotics is from fermented foods including yogurt, kefir, kombucha, kimchi, tempeh and miso.

It is also possible to purchase probiotic supplements. If you are looking elsewhere for products it is best to find ones that have at least 1 billion colony forming units (CFU). Many of these products will have specific bacteria. It is worth doing further research for your specific goals, and below you will find some starting resources:

Cutting Refined Sugar from Diet

It is very common for opioid users to have a high sugar intake, one study suggesting at least double of the general population.132Morabia, A., Fabre, J., Chee, E., Zeger, S., Orsat, E., & Robert, A. (1989). Diet and opiate addiction: a quantitative assessment of the diet of non-institutionalized opiate addicts. British journal of addiction, 84(2), 173-80. http://doi.org/10.1111/j.1360-0443.1989.tb00566.x In addition to the fact that it is addictive in its own right and has other health consequences, there is some evidence from animal models that excessive sugar intake can exacerbate dependence on opioids.133Colantuoni, C., Rada, P., McCarthy, J., Patten, C., Avena, N.M., Chadeayne, A., & Hoebel, B.G. (2002). Evidence that intermittent, excessive sugar intake causes endogenous opioid dependence. Obesity Research, 10(6), 478-88. http://doi.org/10.1038/oby.2002.66 Cutting refined sugars from your diet can make it easier to reduce tolerance to opioids and other substances.

Cannabinoids

Cannabis has been a go to for detox for a long time. It’s effects of helping to relieve anxiety, pain and nausea, and to assist with sleep can provide a lot of assistance especially through acute withdrawal.

Cannabidiol (CBD)

CBD is increasingly sought as a way to manage chronic pain and there is evidence that people who use it rely less on opioids for pain management.134Boehnke, K.F., Litinas, E., & Clauw, D.J. (2016). Medical cannabis use is associated with decreased opiate medication use in a retrospective cross-sectional survey of patients with chronic pain. Journal of pain, 17(6), 739-44. http://doi.org/10.1016/j.jpain.2016.03.002

There is evidence that CBD interacts with the dopamine reward pathway and in animal models has led to lower morphine self-administration.135Katsidoni, V., Anagnostou,. I, & Panagis, G. (2013). Cannabidiol inhibits the reward-facilitating effect of morphine: involvement of 5-HT1A receptors in the dorsal raphe nucleus. Addiction biology, 18(2), 286-96. http://doi.org/10.1111/j.1369-1600.2012.00483.x136Ren, Y., Whittard, J., Higuera-Matas, A., Morris, C.V., & Hurd, Y.L. (2009). Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances. Journal of neuroscience, 29(47), 14764-9. http://doi.org/10.1523/JNEUROSCI.4291-09.2009 One recent small-scale clinical trial in humans showed that people experienced fewer cue-induced cravings for morphine post-opioid withdrawal with the use of between 400 and 800mg of CBD a day.137 Yasmin, H. (2015). Acute and short-term effects of CBD on cue-induced craving in drug-abstinent heroin-dependent humans.https://clinicaltrials.gov/ct2/show/results/NCT01605539?view=results

Another small-scale study showed that people who used CBD smoked 40% fewer cigarettes with fewer nicotine cravings.138Morgan, C.J., Das, R.K., Joye, A., Curran, H.V., & Kamboj, S.K. (2013). Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findings. Addictive behaviors, 38(9), 2433-6. http://doi.org/10.1016/j.addbeh.2013.03.011

One Canadian study that looked at patients who enrolled in medical cannabis programs while using benzodiazepines found that many patients were able to more easily stop benzo use.139Purcell, C., Davis, A., Moolman, N., & Taylor, S. M. (2019). Reduction of Benzodiazepine use in patients prescribed medical cannabis. Cannabis and cannabinoid research, 4(3), 214–218. https://www.liebertpub.com/doi/10.1089/can.2018.0020 Part of the function of CBD in treating benzo withdrawal may be related to its benefits related to both pain, anxiety and its reduction of seizures, one serious symptom of benzo withdrawal. The FDA has approved CBD for two forms of severe epilepsy for its ability to lower the frequency of seizures.

For the reduction of severe acute anxiety, pain, and morphine withdrawal the dosages of CBD used are generally higher than many over the counter products containing CBD. If using CBD to manage withdrawal or severe pain it is recommended to look for CBD oil extracts that can be dosed anywhere from 500mg to 1g a day.

NAD+

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme that is important in cellular metabolism throughout the body. Intravenous (IV) NAD+ has been used since the 1950s to assist with withdrawals from a number of drugs as well as alcohol, and is currently offered in clinics for a number of indications including opioid, stimulant, alcohol, and benzodiazepine withdrawal.

It’s exact mechanisms are not perfectly clear, but it stabilizes the levels of numerous neurotransmitters in the body and has demonstrated reduction of withdrawal and cravings.

While IV treatment with NAD+ is the most direct and significant way of increasing levels in the body, it is also possible to use NAD+ at home, which can reduce dependency and cravings, or post-acute symptoms for alcohol, opiates or other substances.

Recommended dosages for home use are at least 500mg a day. GetCleanSupplements.com offers both fast-melting sublingual NAD+ tablets that are designed to bypass gastrointestinal destruction and deactivation, as well as an NAD+ nasal spray that has more immediate effect.

Ibogaine Boosters

Ibogaine has a number of beneficial effects in the body. Its role in mitigating withdrawal symptoms might happen by a few different mechanisms, but not least of them is desensitizing the dopamine system. This same effect can be beneficial even when you are not going through acute withdrawal, for PAWS and for depression.

In addition, ibogaine is known to stimulate the release of glial cell-derived neurotrphic factor (GDNF) and brain-derived neurotrophic factor (BDNF), both of which can contribute to dopamine repair and generally to neuroplasticity. The state of neuroplasticity is basically the brain’s ability to adapt from one state to another. Withdrawal is an extreme example of a state change, but being able to continue to work with ibogaine in various kinds of doses later can continue to assist in this shift. Again, it is helpful to think about recovery post ibogaine as a long-term process rather than an overnight event.

There are obvious legal restrictions that limit the availability of ibogaine in certain places, including the United States and Canada. Ceiba collaboratese with Iboga Revolution to provide psychospiritual retreats and private sessions that are ideal for people following up after ibogaine-assisted detox, or who are in later stages by other means. We provide space for flood doses or smaller booster doses in a setting that is both medically supported and expertly facilitated to help explore other dimensions of ibogaine’s psychospiritual effects.

Additional Support Post-Withdrawal

As mentioned above, these tools are primarily designed at treating the body, which is an important and critical aspect in making recovery possible for many people. It is an focus that is definitely not taken into consideration enough during recovery. However, the physical aspects of withdrawal only form a part of the complete strategy for making changes from addiction and other kinds of support can be a critical part of the process. Ibogaine treatment, aftercare, various other kinds of treatment programs, and other recovery communities all provide an immense amount of support.

There are many options for programs that will be open to, or knowledgeable about these methods, if they don’t already actively employ them themselves. I highly recommend looking at my list of options for ibogaine aftercare, which includes numerous kinds of recovery groups that are available locally as well as online. In our twice-monthly Life After Ibogaine groups we often discuss how people are using these as well as other strategies especially post-treatment.

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