作者：Marlene Busko
出處：WebMD醫學新聞
December 12, 2008(佛州波卡雷登) — 研究者報告指出，在古柯鹼使用者的實驗室研究中，黃體素可減少慾望，而且感覺就像被古柯鹼刺激一樣。
此外，黃體素也減少了古柯鹼引起的收縮壓升高，但是它不會減少高潮的感覺、降低古柯鹼引起的心律或者降低收縮壓值升高。
相較於婦女對古柯鹼的反應，男性有較大的收縮壓值升高和較快的心搏，且感覺比較有高潮和刺激，但是婦女的癮頭比較大。
這些結果來自黃體素的非適應症研究，研究對象是38名古柯鹼依賴病患，主要研究者、明尼蘇達大學的Sheila Specker醫師於美國成癮精神科學會第19屆年會暨研討會中發表結果。
她向與會代表表示，此次較多研究對象的試驗提供了黃體素用於古柯鹼之生理效應和主觀效應效果的額外支持。不過，她指出，需要持續的研究，以探討性別差異對於藥癮的差別，以及藥癮對月經的影響。
【主要問題】
古柯鹼濫用仍然是男性和女性的一大問題，而藥物治療效果有限。
之前的研究確認了古柯鹼使用模式和生理效果的兩性差異，認為性荷爾蒙在藥癮和成癮性上有所影響。
黃體素具有γ-胺基丁酸(GABA)致效劑活性代謝物，認為或許可以藉由減少藥物的多巴胺性質而降低古柯鹼癮頭。
此外，臨床前研究顯示，黃體素減少了動物的古柯鹼自我取食，許多臨床研究支持這些發現；不過，這些初步研究並未區別雌激素與黃體素，且樣本少、或者只探討單一性別。
為了檢視黃體素對古柯鹼慾望、自我取食、生理反應等的效果，研究者進行了一個實驗室內的試驗。
這項研究包括了21個男性和17個女性，平均年紀為40歲，使用古柯鹼達15年。在之前的30天內，這些研究對象曾經使用古柯鹼、酒精與大麻，平均值分別為15.6、6.5、4.3 天。
研究對象參加兩次住院4天的實驗小組，兩次間隔一個月。
研究對象在第1天被隨機分派接受200或者400 mg 的黃體素或者安慰劑。在第2天，他們適應這個藥物療法。在第3和4天，他們參加一個3小時的實驗，在實驗中，他們可以每30分鐘決定一次，接受5塊美金或者一劑量的古柯鹼。
在一個月之後，這些研究對象回來接受一次類似的實驗。
初級結果變項為古柯鹼效果問卷(Cocaine Effects Questionnaire)中，對於癮頭、刺激感、最後一次劑量效果的感覺、高潮感覺、心搏快速等的反應；生理測量包括血壓和脈搏；以及使用古柯鹼的劑量。
【慾望明顯略降】
黃體素對於使用劑量次數沒有效果，它明顯降低慾望(P< .001)，感覺較不刺激(P= .027)；此外，它也降低了收縮壓(P< .001)，但是沒有降低舒張壓BP或者心律或者減少高潮感。
Specker醫師表示，許多因素可能與使用古柯鹼的決定有關，雖然研究結果明顯，但是反應算小。
她表示，實驗室模式是用來研究與區別藥物效果的有用方法，但是研究對象可能因為其他因素而影響決定自我取食古柯鹼。後續研究應探討雌激素、GABA致效劑與鴉片類阻斷劑的影響，且應擴及包含男性和女性的門診病患。
本研究接受國家藥物濫用研究中心的支持。Specker醫師宣稱沒有相關資金上的往來。
美國成癮精神科學會第19屆年會暨研討會。海報發表小組1。2008年12月7日。
AAAP 2008: Progesterone May Diminish Cocaine Craving
By Marlene Busko
Medscape Medical News
December 12, 2008 (Boca Raton, Florida) — In a laboratory study of cocaine users, progesterone reduced craving and the feeling of being stimulated by cocaine, researchers report.
Progesterone also decreased cocaine-induced systolic blood pressure (BP) elevation, but did not diminish the feeling of being high, lower cocaine-induced heart rate, or lower the elevation of diastolic BP.
Men had a greater increase in diastolic BP and more heart racing, and reported feeling higher and more stimulated than women in response to cocaine, whereas women had more craving.
These results from an off-label study of progesterone in 38 cocaine-dependent subjects were presented here at the American Academy of Addiction Psychiatry 19th Annual Meeting and Symposium by primary investigator Sheila Specker, MD, from the University of Minnesota, in Minneapolis.
"This larger within-subjects design provides additional support for an effect of progesterone on subjective and physiological effects of cocaine," she told the conference delegates.
However, she added, there is a need for continued investigation into sex differences and variability in craving and use across the menstrual cycle.
Major Problem
Cocaine abuse remains a major problem in men and women, and medications have had minimal effect.
Previous research identified sex differences in cocaine-use patterns and physiological effects, suggesting that sex hormones play a role in craving and addiction.
Progesterone, which has a gamma-aminobutyric acid (GABA) agonist active metabolite, was proposed as an agent that might decrease cocaine craving by reducing the dopaminergic properties of the drug.
In addition, preclinical research has shown that progesterone decreases self-administration of cocaine in animals, and several clinical studies support these findings. However, these earlier studies did not always separate the effects of estrogen from progesterone, had small sample sizes, or looked at a single sex.
To examine the effect of progesterone on cocaine craving, self-administration, and physiological response, the researchers conducted an in-laboratory trial.
The study included 21 men and 17 women with a mean age of 40 years who had been using cocaine for 15 years. The subjects had used cocaine, alcohol, and cannabis an average of 15.6, 6.5, and 4.3 days of the previous 30 days, respectively.
The subjects participated in 2 in-patient 4-day experimental sessions, 1 month apart.
Participants were randomized to receive 200 or 400?mg of progesterone or placebo on day 1. On day 2, they adapted to this medication. On days 3 and 4, they participated in 3-hour experiments in which every 30 minutes they could choose to receive either $5 or a dose of cocaine.
The subjects returned for a second similar experimental session 1 month later.
The primary outcome variables were Cocaine Effects Questionnaire responses about craving, feeling stimulated, feeling the effect of the last dose, feeling high, or having a racing heart; physiological measures of blood pressure and pulse; and doses of cocaine taken.
Significant, Small Decrease in Craving
Progesterone had no effect on the number of doses taken. It did significantly decrease craving (P?< .001), and subjects felt less stimulated (P?= .027). It also lowered systolic BP (P?< .001), but did not lower diastolic BP or heart rate or diminish the feeling of being high.
"Many factors are likely associated with the decision to use cocaine," said Dr. Specker, noting that although the results were significant, the response was small.
"A laboratory model is a useful method to study and isolate the effects of medications, but the subjects' decisions to self-administer cocaine may be influenced by other factors," she said. Future research should investigate the roles of estrogen, GABA agonists, and opioid blockers, and should be larger outpatient studies with more women.
The study was supported by a grant from the National Institute on Drug Abuse. Dr. Specker has disclosed no relevant financial relationships.
American Academy of Addiction Psychiatry 19th Annual Meeting and Symposium. Paper Presentation Session 1. December 7, 2008.
[ 本帖最後由 goodcat1111 於 2008-12-23 10:35 編輯 ] |
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