Table 1.
Clinical and preclinical studies reporting the effect of the KD on SUD.
| Substance | Clinical/preclinical | Methods of KD | Major outcome | References |
|---|---|---|---|---|
| Clinical study | ||||
| Alcohol | Patients with AUD (Standard American diet, n = 14; KD, n = 19) | 80% fat, 15% protein, and 5% carbohydrates; 3 weeks | Reduced alcohol craving and withdrawal symptoms (needed less benzodiazepines) | (28) |
| Preclinical study | ||||
| Alcohol | Male OF1 mice (alcohol oral self-administration paradigm) | 90.5% kcal from fat, 0.3% kcal from carbohydrates and 9.1% kcal from protein; 6.7 kcal/g; 4 weeks | Decreased oral ethanol self-administration | (30) |
| Alcohol | Male Wistar rats (alcohol self-administration) | 5% of calories was from protein, 2% was from carbohydrates, and 93% was from fat; 8 weeks | Reduced alcohol consumption | (28) |
| Alcohol | Male Sprague Dawley rats (alcohol oral gavage for 6 days) | 93% calories from fat, 5% from protein, 2% from carbohydrate; 10 days | Decreased alcohol withdrawal symptoms (“rigidity” and “irritability”) | (31) |
| Alcohol | Male C57BL/6NTac mice (intermittent alcohol exposure for 3 weeks using liquid diet) | 93% calories from fat, 5% from protein, 2% from carbohydrate; 3 weeks | Decreased alcohol withdrawal symptoms (convulsions and anxiety-like behavior) | (32) |
| Cocaine | Sprague–Dawley rats (daily intraperitoneal injections of 15 mg/kg cocaine for 1 week, were drug free for a subsequent week, and then received a final challenge injection of 15 mg/kg cocaine) | 93% kcal from fat, 2% kcal from carbohydrates and 5% kcal from protein; 5 weeks | Decreased cocaine-induced stereotyped responses; disrupted sensitization of ambulatory responses | (29) |
| Cocaine | Male OF1 mice (intraperitoneal injections of 10 mg/kg cocaine induced CPP procedure) | 90.5% kcal from fat, 0.3% kcal from carbohydrates and 9.1% kcal from protein; 8 or 10 weeks | Reduced the number of sessions required to extinguish the drug-associated memories and blocked the priming-induced reinstatement. | (33) |
| Cocaine | Male C57BL/6J (intraperitoneal injections of 10 mg/kg cocaine induced CPP procedure; after extinction for 3 weeks, the mice received a priming dose of 7.5 mg/kg cocaine and underwent a reinstatement test) | 90.5% kcal from fat, 0.3% kcal from carbohydrates and 9.1% kcal from protein; 3 weeks | Disrupted cocaine CPP reinstatement | (34) |
| Oxycodone | C57BL/6J mice (oxycodone self-administration) | 93.4% fat, 4.7% protein, and 1.8% carbs; 4–14 days | Increased oxycodone-induced locomotor activity and enhanced antinociceptive effects of oxycodone; decreased oxycodone self-administration in male mice | (35) |
KD, Ketogenic diet; SUD, substance use disorders; AUD, alcohol use disorders.