Sunday, December 26, 2010

A NEW ERA IN THE USE OF DRUGS IN OBSTETRICS - Primal Health Research Newsletter Vol 18. No 2

PRIMAL HEALTH RESEARCH


A NEW ERA IN HEALTH RESEARCH

Published quarterly by Primal Health Research Centre

Charity No.328090

72, Savernake Road, London NW3 2JR

michelodent@googlemail.com

Winter 2010 Vol 18. No2

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A NEW ERA IN THE USE OF DRUGS IN OBSTETRICS


In a typical modern birth, the release of natural oxytocin is replaced by an intravenous drip of synthetic oxytocin, while an epidural analgesia is a substitute for the physiological systems of protection against labour pain, particularly the release of endorphins. Until now pharmacological assistance in childbirth has been based on a simplistic principle, which is hormonal replacement. Even if, in the near future, the basic needs of labouring women are universally accepted, and even if non-pharmacological methods for facilitating the physiological processes develop, one cannot imagine the end of pharmacological assistance in childbirth.

Learning from clinical observation


One can anticipate, however, the development of a new basis for this kind of assistance. This new step will imply that the specifically human handicap in childbirth is understood. In other words, it implies that the concept of neocortical inhibition is not ignored any more.

This leads me to recall how, in 1964, I suddenly and unexpectedly understood the most important aspect of birth physiology. A friend of mine, a medical doctor working for a French pharmaceutical firm, gave me some samples of the recently synthesized Gamma-Hydroxybutyric acid (GHB). In the context of the 1960s he was already in a position to explain that it was an analogue of GABA (Gamma-Aminobutyric acid) and that it could not be dangerous since it was an integral part of the mammalian central nervous system.1 This newly commercialized substance was presented as a sedative medication and as a promising agent in anaesthesiology. My friend added that, according several preliminary reports, it was also sharing the properties of oxytocin.

This is how I had the experience of births with drips of what is called in France Gamma-OH. With such a drip labouring women were getting completely crazy, shouting in the corridors, pulling out their intravenous needle, scaring the midwife...but the baby was born right away. Of course such scenes we unacceptable in a hospital setting and we had to be cautious with possible unreported negative side effects. The main result of this audacious experiment – that we had to stop immediately – was a sort of revelation: when the activity of the neocortex is eliminated, human beings have more similarities with the other mammals: this is what makes birth easy. I had understood the concept of neocortical inhibition and the solution nature had found to overcome the human handicap. I had understood that the neocortex of a labouring woman must not be stimulated.

Since that time we have learned a lot about the inhibitory effects of GHB and GABA.2 In fact GHB has found limited clinical use as an anaesthetic agent. On the other hand, a widespread interest for this drug developed recently, because it has emerged as a major recreational drug and public health problem. Illicit forms are available under a number of names, such a G, or liquid ecstasy. Its property to neutralise neocortical inhibitions explains the notoriety of this “date-rape drug” – in other words a compound used to facilitate sexual assault.

My understanding of the effects of neocortical inhibition in childbirth has been reactivated about ten years later through another significant anecdote. A young mother was celebrating the birth of her one day old baby in a double bedroom. Her neighbour was in prelabour. This is how glasses of champagne were exchanged. The effect of champagne was so spectacular that a baby was born through a ‘fetus ejection reflex’ on the way to the birthing room.3 It is well known that champagne is a special wine. Thanks to the bubbles, alcohol is brought immediately to the brain. The ability of alcohol to change human consciousness has been known for ages. Today we understand how alcohol works: one of its effects is to bind to the GABA receptors.4

I also learned a lot from the easy way schizophrenic women were giving birth before the widespread use of powerful antipsychotic treatments. It has been demonstrated that unmedicated schizophrenic people have neocortical inhibition deficits. Interestingly powerful antipsychotic drugs such as clozapine tend to potentiate the effects of GABA.5

Learning from word of mouth

It is significant that the psychedelic drugs used for their spiritual virtues have also been used to facilitate labour. This is the case of cannabis, which has been, and still is, a Holy plant in many cultures all over the world. Although some European countries, Canada, and some US states have legalised medical cannabis, it is only through anecdotes and word of mouth that we are learning about its actual effects in the particular case of the birth process. The biochemical effects of the cannabinoids – the most prevalent psychoactive substances in cannabis – have been widely studied. In 1990, the discovery of cannabinoid receptors located throughout the brain and body, along with endogenous cannabinoid neurotransmitters, suggested that cannabis affects the brain in the same manner as a naturally occurring brain chemical. Cannabinoids play an easy to observe role in neocortical activity, with a distortion of the perception of time and space; furthermore, they affect pain transmission by interacting with the system of endorphins.6 Their effects on the birth process can therefore be easily interpreted.

The Daime, a drink known generically as Ayahuasca, is another typical example of a drug used for both its spiritual virtues and its reputation to facilitate the birth process. It is the basis of a spiritual practice, the Santo Daime, which was founded in the Brazilian Amazonian state of Acre in the 1930s and became a worldwide movement in the 1990s. Because the Daime is legal for religious use in Brazil, some midwives know about the effects of this drug during labour and do not hesitate to report their observations. This decoction is made from two or more plants, such as the leaves of ‘Psychotria viridis’, which have high concentrations of the psychoactive compound dimethyltryptamine. Not only is this substance found in many plants, but it is also created in small amount by the human body during normal metabolism. Its natural function remains undetermined. The stomach normally digests it, so that it does not reach the brain if consumed orally, except if it is mixed with a ‘monoamine oxidase inhibitor’ (MAOI). Interestingly the Daime also contains a vine, such as Banisteriopsis caapi, which is a source of MAOI. One can wonder how the natives found this combination without knowing anything about the interaction in the stomach of dimethyltryptamine and MAOI !


All drugs have side effects.

The point is not to promote the use in childbirth of GHB, marijuana, daime, or even champagne. It is much more to learn from the effects of drugs that do not belong to the official pharmacopoeia, and to realise that as long as birth physiology is not understood as a chapter of brain physiology, pharmacological assistance in childbirth is reduced to hormonal replacement. The current dominant approach is based on the use of substitutes for oxytocin, endorphins, and prostaglandins. It is possible that in the near future a greater importance given to the concept of neocortical inhibition, new questions about plastic related substances such as phtalates, and new questions about the transfer of synthetic oxytocin across the placenta and the fetal blood brain barrier will justify a more cautious use of what is today the main component of pharmacological assistance in childbirth.

However all drugs have side effects and it takes time to evaluate risks and benefits of new pharmacological agents. In the case of drugs that interfere with brain functions, it will be essential to think long-term, in other words to take into account the primal health research perspective. This is suggested by animal experiments, such as those by Carol Kellogg, who studied the long-term consequences on the offspring of diazepam – a widely used sedative drug acting on the GABA receptors. One of the significant conclusions of her experiments is that exposure to this drug at the end of fetal life induces behavioural effects that do not become apparent in exposed animals until young adult ages.7 There are other significant conclusions of these series of studies suggesting the need to think long-term when manipulating brain receptor during the early phases of development. For example if male rats have been exposed to diazepam before being born, the expected adolescent surge of testosterone does not occur.8

The importance of keeping in mind the possible long-term effects of drugs used during the perinatal period is also a lesson to learn from studies by Bertil Jacobson and Karin Nyberg about the risk factors for drug addiction: opiates and nitrous oxide used during labour appear as risk factors in all their studies.9,10,11,12

Finally, even if a more cautious approach regarding pharmacological assistance in obstetrics is probable during the twenty first century, and even if the concept of in-labour non-emergency caesarean is better understood, the priority will always be to rediscover the basic needs of labouring women, as long as the main objective is to facilitate in our societies the release of an abundant flow of love hormones in critical periods of human life.

Michel Odent

References:

1 – Laborit H. 4-hydroxybutyrate. Int J Neuropharmacol 1964;32: 433-451

2 – Snead OC, Gibson M. Gamma-hydroxybutyric acid. NEJM 2005; 352:2721-2732.

3 – Odent M. Champagne and the fetus ejection reflex. Midwiferytoday

4 - Santhakumar V, Wallner M, Otis TS. Ethanol acts directly on extrasynaptic subtypes of GABAA receptors to increase tonic inhibition. Alcohol 2007; 41 (3): 211–21.

5 - Liu SK, Fitzgerald PB, Daigle M, et al. The relationship between cortical inhibition, antipsychotic treatment, and the symptoms of schizophrenia. Biol Psychiatry. 2009 Mar 15;65(6):503-9. Epub 2008 Oct 31.

6 - Fattore L, Cossu G, Spano MS, et al. Cannabinoids and reward: interactions with the opioid system. Crit Rev Neurobiol. 2004;16(1-2):147-58.

7 - Kellogg CK, Yao J, Pleger GL. Sex-specific effects of in utero manipulation of GABA(A) receptors on pre- and postnatal expression of BDNF in rats. Brain Res Dev Brain Res 2000 Jun 30;121(2):157-67.

8 - Kellogg CK, Kenjarski TP, Pleger GL, Frye CA. Region-, age-, and sex-specific effects of fetal diazepam exposure on the postnatal development of neurosteroids. Brain Research 2006 Jan 5;1067(1):115-25. Epub 2005 Dec 22.

9 - Jacobson B, Nyberg K. Obstetric pain medication and eventual adult amphetamine addiction in offspring. ACTA Obstet. Gynecol. Scand. 1988; 67:677-682

10 - Jacobson B, Nyberg K. Opiate addiction in adult offspring through possible imprinting after obstetric treatment. BMJ 1990;301:1067-70.

11 - Nyberg K, Allebeck P, Eklund G, Jacobson, B. Socio-economic versus obstetric risk factors for drug addiction in offspring. Brit. J. of Addiction 1992; 87:1669-1676

12 - Nyberg K, Allebeck P, Eklund G, Jacobson, B. Obstetric medication versus residential area as perinatal risk factors for subsequent adult drug addiction in offspring. Paed. and Perinatal Epid. 1993;7: 23-32.

[This article has been posted with permission of the author, Michel Odent. ]

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