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Specifically, there are differences anatomically between men and women that have a strong effect on substance pharmacodynamics, pharmacokinetics and also metabolism.Specific variances exist, and those differences create differing responses depending on the substance in question.1. Women's bodies store 20% overall body fat at minimum if diet and exercise permit. The evolutionary reason for this is that women under 20% body fat are vastly more likely to miscarry or deliver a child early. This 20% body fat cushion is referred to as the "Reproductive Cushion," in the medical literature. Many substances are lipophilic, meaning that they are stored in body fat and can potentially be released from fatty tissues. From a "healthy" BMI standpoint, this difference in body fat is more than double that of a healthy male.2. Women have a different water balance than men as well as a different distribution of bodily fluid. This is controlled largely by the interplay of Oestradiol and Progesterone and their analogues either synthetic or endogenous. This variability of water balance and distribution can dramatically affect substance concentrations, creating differing responses to the same dose of a substance. See:Sex Hormone Effects on Body Fluid Regulation3. Women's normal hormone fluctuations have an effect on mood, anxiety, tolerance and intoxication. According to research published in "Sex Differences in Drug Abuse, Frontiers in Neuroendocrinology, 2008," females of reproductive age have a more difficult time quitting smoking during the late luteal phase due to declining estrogen and progesterone levels, however:"estradiol decreases anxiety and negative affect, thereby alleviating some of the negative consequences of smoking cessation."4. Other physical variances between the genders have significant effects on how individuals respond to substance abuse and addiction. Women have a lesser amount of the enzyme alcohol dehydrogenase (which destroys ethanol) in the stomach than men, this coupled with variable fluid volume and distribution depending on menstrual phase can create markedly different levels of intoxication in women exposed to the same amount of alcohol as men. According to the same study referenced above as well as several other well cited and carefully constructed studies, there are other assertions to be made such as:For example, women become addicted to alcohol more rapidly than do men [142], and brain atrophy develops more rapidly in women than in men (other negative medical consequences involve the heart, muscle and liver which are also compromised more rapidly in women than in men [86]).In women, the subjective effects of stimulants vary across the menstrual cycle [66-68]. For example, several of the positive subjective effects of d-AMPH such as euphoria, desire, increased energy and intellectual efficiency are potentiated during the follicular phase (when estradiol levels are low at first and rise slowly; progesterone levels are low) relative to the luteal phase (when estradiol levels are moderate and progesterone levels are high). Additionally, administration of estradiol during the follicular phase further increases the subjective effects of d-AMPH [67]. In contrast, the subjective effects of psychomotor stimulant drugs are negatively correlated with salivary progesterone levels in women [136], and progesterone administered during the follicular phase has been reported to attenuate the subjective response to repeated self-administered cocaine [44,45,117].As you can see, there are numerous differences and a great deal of ongoing research on this subject, much information of value may be gleaned from the studies referenced below.I hope this answers your question adequately.References:1. Alele PE, Devaud LL. Sex differences in steroid modulation of ethanol withdrawal in male and female rats. Journal of Pharmacology & Experimental Therapeutics. 2007;320:427–36. [PubMed]2. Andersen SL, Rutstein M, Benzo JM, Hostetter JC, Teicher MH. Sex differences in dopamine receptor overproduction and elimination. Neuroreport. 1997;8:1495–8. [PubMed]3. Anglin MD, Hser YI, McGlothlin WH. Sex differences in addict careers. 2. 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