Finasteride and Cannabis Interaction Profile: What the Evidence Actually Shows

What happens when you take finasteride and cannabis together?

CBD competitively inhibited CYP3A4 in laboratory assays using microsomes that overexpress human P450 enzymes [1], and finasteride is extensively metabolized in the liver, mainly by CYP3A4 [2]. Whether that enzyme inhibition changes finasteride levels in people has not been measured.

The labels read differently. The Propecia and Proscar drug interactions sections state that no drug interactions of clinical importance have been identified and that finasteride does not appear to affect the cytochrome P450-linked drug-metabolizing enzyme system; the compounds tested in humans were antipyrine, digoxin, propranolol, theophylline and warfarin [2][3]. Cannabis is not among them.

Finasteride comes as a 1 mg tablet (Propecia) for male pattern hair loss in men only [5] and a 5 mg tablet (Proscar) for symptomatic benign prostatic hyperplasia [6].

How finasteride is cleared

A 1 mg tablet is about 65% bioavailable, and food does not change its absorption [2]. Peak levels occur 1 to 2 hours after a dose, about 90% of the drug is protein bound, and it is extensively metabolized in the liver, mainly by CYP3A4; two metabolites carry no more than 20% of finasteride's activity [2]. Mean terminal half-life is about 5 to 6 hours in men 18 to 60 and about 8 hours in men over 70 [2].

The hormonal effect outlasts the plasma level. The Type II 5-alpha-reductase enzyme complex turns over slowly, roughly 30 days, so DHT suppression continues well past the point where the drug has left the blood [2].

CYP3A4 is named as finasteride's metabolic route in the clinical pharmacology section, but drugs that inhibit or induce CYP3A4 are not addressed in the interactions section [2].

What cannabis does to the same enzymes

In laboratory assays, CBD competitively inhibited CYP3A4, CYP2B6, CYP2C9, CYP2D6 and CYP2E1. THC competitively inhibited CYP1A2, CYP2B6, CYP2C9 and CYP2D6, and two major THC metabolites also inhibited CYP2B6, CYP2C9 and CYP2D6 [1]. That puts CBD on the same enzyme that clears finasteride.

A systematic review of cannabinoid enzyme data found that THC is metabolized partly by CYP2C9 and CYP3A4 and CBD partly by CYP2C19 and CYP3A4, and that a ketoconazole interaction study with an oromucosal cannabis extract supports CYP3A4 as a significant pathway for both [4]. The same review concluded that the inhibition and induction data generally reflect a low risk of clinically significant drug interactions with most use, while noting that specific human data are lacking [4].

The two findings come from different kinds of evidence: one describes what CBD does to an enzyme in isolated microsomes, the other describes what was seen when finasteride was given with five specific medicines to people [1][2].

Does finasteride change cannabis?

The Propecia label states that finasteride does not appear to affect the cytochrome P450-linked drug-metabolizing enzyme system [2]. THC and CBD are themselves partly cleared by CYP3A4 [4]. That label statement is about finasteride's effect on the enzyme system as a whole, not a measured cannabinoid level, and the interactions section covers the five compounds named above [2].

Sexual side effects: each on its own

In three 12-month placebo-controlled trials of finasteride 1 mg (945 men on finasteride, 934 on placebo, aged 18 to 41), decreased libido was reported by 1.8% vs 1.3%, erectile dysfunction by 1.3% vs 0.7%, and ejaculation disorder by 1.2% vs 0.7%. Overall, 36 of 945 men (3.8%) reported one or more of these versus 20 of 934 (2.1%) on placebo (p=0.04), and discontinuation for drug-related sexual events was 1.2% vs 0.9% [2]. A meta-analysis of 15 randomized placebo-controlled trials in 4,495 men with androgenetic alopecia found a relative risk of sexual dysfunction of 1.66 (95% CI 1.20 to 2.30) for finasteride 1 mg [9]. A separate review of 34 finasteride trials for hair loss found that none had adequate safety reporting and that funnel plots suggested under-detection of sexual adverse effects [10].

Cannabis affects sexual function too. A review of cannabinoid effects on sexual behavior and gonadal hormones describes dose-dependent effects on sexual behavior and arousability, with animal evidence pointing mainly to reduced male sexual motivation and erectile function, and reports that cannabinoid-induced inhibition of male sexual behavior appeared independent of concurrent testosterone declines [7].

The finasteride percentages above are for finasteride alone.

Mood

The Propecia label lists depression and suicidal ideation and behavior as postmarketing reports [2]. The Proscar label lists depression and suicidal ideation [3]. Both labels state that these reports are voluntary, come from a population of uncertain size, and cannot reliably establish a causal relationship [2][3]. Neither the current Propecia nor Proscar label has a boxed warning for these events [2][3]. The wording change followed an FDA safety labeling change order of May 31, 2022, and the Propecia supplement approved 08/01/2022 changed the postmarketing wording to "depression, suicidal ideation and behavior" [11].

Observational data in older men are mixed. In Ontario, 93,197 men aged 66 or older starting a 5-alpha reductase inhibitor were compared with matched unexposed men: suicide HR 0.88 (95% CI 0.53 to 1.45), self-harm HR 1.88 (1.34 to 2.64) confined to the first 18 months, and depression HR 1.94 (1.73 to 2.16) in the first 18 months [12]. In a Swedish register cohort of 2,236,876 men aged 50 to 90, finasteride starters had a depression HR of 1.61 (1.48 to 1.75) and no significant association with suicide (HR 1.22, 0.99 to 1.49) [13]. Both studies were mostly older men treated for prostate enlargement, not young men taking 1 mg for hair loss.

On the cannabis side, a systematic review of 12 prospective studies (11,959 people) looked specifically at people who already met criteria for an anxiety or mood disorder at baseline. Recent cannabis use was associated with higher symptom levels over time in 11 of the studies and with less improvement from treatment in 10, and the authors noted the observational designs and sample biases [8]. Those findings do not establish a general mood effect of cannabis in people without such a disorder.

Persistent sexual effects listed in the labels

The Propecia label says that in the hair-loss trials, sexual adverse reactions resolved in men who discontinued because of them and in most men who continued [2]. The postmarketing section also lists sexual dysfunction that continued after stopping treatment (erectile dysfunction, libido, ejaculation and orgasm disorders) and male infertility or poor seminal quality, with normalization or improvement of seminal quality reported after discontinuation [2]. These are postmarketing reports, which the label says cannot reliably establish causality [2].

For the 5 mg dose, the Proscar label reports higher first-year rates in the 4-year PLESS trial (1,524 men on finasteride, 1,516 on placebo): impotence 8.1% vs 3.7%, decreased libido 6.4% vs 3.4%, and decreased ejaculate volume 3.7% vs 0.8% [3]. In years 2 to 4 there was no significant difference between groups in impotence, decreased libido and ejaculation disorder [3].

Where that leaves the question

Finasteride is cleared mainly by CYP3A4 [2]; CBD inhibits that enzyme in the laboratory [1]; a systematic review judged cannabinoid enzyme interactions low-risk for most use [4]; and neither label lists cannabis among the tested compounds [2][3]. Meanwhile, finasteride trials report sexual side effects [2], a cannabis review describes dose-dependent sexual effects including animal evidence on erectile function [7], and a review of people with existing anxiety or mood disorders associates recent cannabis use with worse symptoms over time [8]. Because the effects overlap, it can be hard to tell the cause when symptoms appear in a man using both, and the evidence does not show that the combination produces more of them.