Scutellaria lateriflora / Skullcap

Skullcap Has Anxiolytic and Mood-Enhancing Effects in Healthy Subjects 
Reviewed: Brock C, Whitehouse J, Tewfik I, Towell T. American skullcap (Scutellaria lateriflora): A randomised, double-blind placebo-controlled crossover study of its effects on mood in healthy volunteers [published online ahead of print July 22, 2013]. Phytother Res. doi: 10.1002/ptr.5044.

Skullcap (Scutellaria lateriflora, Lamiaceae) has been used traditionally to treat anxiety, stress, and related disorders. While there is some supporting experimental and human evidence, definitive results from high-quality clinical trials evaluating skullcap for anxiety are lacking. Hence, the purpose of this randomized, double-blind, placebo-controlled, crossover study was to evaluate the effect of skullcap on mood.

Healthy subjects (n=31, aged 18-75 years) were recruited via advertisements for participation in this study conducted in New Cavendish, London. Inclusion criteria were persistent stress, anxiety, mood swings, irritability, poor sleep, or difficulty in coping; however, non-anxious participants were also eligible. Exclusion criteria were alcohol or recreational drug dependence; known hypersensitivity to any herbal medicines; use of medication (other than a contraceptive pill) affecting the central nervous system (CNS) within the month preceding the study; a history of psychiatric disorders; any serious medical condition; moderate-to-high depression (Hospital Anxiety and Depression Scale [HADS-D] scores ≥ 9); very severe anxiety (initial scores > 40 on Beck’s Anxiety Inventory [BAI]); pregnancy or lactation; or abnormal blood alanine aminotransferase (ALT) level (a liver enzyme).

Subjects took either placebo or 350 mg freeze-dried skullcap aerial parts (Eclectic Institute, Inc.; Sandy, Oregon) three times per day for 14 days. Freeze-dried stinging nettle (Urtica dioica, Urticaceae) leaf capsules (300 mg) were chosen as the placebo as they have no known effects on the CNS and were similar in appearance, taste, and smell to the skullcap capsules, according to the authors. (Although significant CNS effects have not been reported for stinging nettle, some may question its status as an inactive comparison.) The skullcap capsules contained freeze-dried aerial parts, not a standardized extract. As skullcap adulteration with hepatotoxic Teucrium species (Lamiaceae) has been reported — and Scutellaria lateriflora (Lamiaceae) is known to be substituted with other Scutellaria species1,2 — the identity and chemical composition of the experimental material was assessed in comparison to a voucher specimen (American Herbal Pharmacopoeia; Scotts Valley, California) using high-performance liquid chromatography. The Teucrium marker compound verbascoside was not detected, and the samples contained relatively high levels of baicalin (11.71 ± 1.16 mg/g), baicalein (7.67 ± 0.89 mg/g), and small amounts of wogonin (0.65 ± 0.06 mg/g).

Following a seven-day washout period, the subjects were crossed over to the other treatment. At baseline and at the end of each treatment period, subjects completed the BAI and the Profile of Mood States (POMS) standard questionnaire. In addition, blood pressure and pulse were recorded, and blood was drawn to measure ALT. The subjects also were asked to complete a diary recording any positive or negative experiences.

The study was well blinded; subjects did not notice any difference in taste, smell, or appearance between treatments. At baseline, 11 subjects had minimal anxiety (BAI scores 0-7), 14 were mildly anxious (BAI scores 8-15), three were moderately anxious (BAI scores 16-25), and three had severe anxiety (BAI scores ≥ 26). Hence, the anxiety level in the study population was relatively low (81% had BAI scores ≤ 15). Despite randomization (group 1 starting with placebo followed by skullcap intervention and group 2 with treatments in the reverse order), by chance, all six subjects with the highest BAI scores were assigned to the same group. Therefore, there was a significant difference between groups at baseline.

Compared with baseline, subjects taking skullcap had a significant improvement on BAI (P=0.003) when compared to placebo treatment. The results of the POMS indicated that skullcap did not cause a reduction in energy or cause fatigue. Evaluating the total mood disturbance with the POMS, there was no between-group difference; however, skullcap treatment significantly decreased symptoms compared with baseline (P<0.001), while the placebo treatment did not significantly change from baseline. The symptom diaries revealed that five of 26 subjects had resolution or improvement in chronic conditions (irritable bowel syndrome, mastalgia, dysmenorrhea, hay fever, and eczema) during skullcap treatment but not during placebo treatment.

There were no differences between groups in ALT levels, blood pressure, or pulse. Seven subjects reported adverse events (AEs) during treatment with skullcap; however, it was uncertain whether the AEs could be attributed to skullcap. The reported AEs were vivid dreams (n=1), feeling “spaced out” (n=1), mild digestive disturbances (n=4), and constant taste of salt in the mouth (n=1).
There appeared to be a carryover effect of skullcap, which indicates that the seven-day washout period was not long enough. This could have affected the between-treatment group findings (i.e., an underestimation of effect when skullcap was taken before placebo). Alternately, the significant changes from baseline but not between treatment groups could indicate that there was either a strong placebo effect or the benefit of skullcap was small.

Despite these factors, the authors conclude that skullcap has anxiolytic and mood-enhancing effects in some individuals without a reduction in energy or cognition. They also note the safety of skullcap in this study based on the lack of significant changes in blood pressure or liver enzyme levels; however, “[t]he limitations of carryover effect, generally low anxiety scores and differences in anxiety levels between groups at baseline (p = 0.022), may have reduced the chances of statistical significance in this study.” In addition, the treatment duration may have been too short; typically, pharmaceutical anxiolytics must be taken for at least two weeks before statistically significant improvement is seen. Perhaps the greatest shortcoming is the use of normal volunteers rather than patients who were diagnosed with an anxiety disorder.
—Heather S. Oliff, PhD

References
1.     Foster S. Adulteration of skullcap with American germander. HerbalGram. 2012;93:34-41. Available at: http://cms.herbalgram.org/herbalgram/issue93/FEAT_skullgerm.html. Accessed April 7, 2014.
2.     Upton R, ed. Skullcap Aerial Parts Scutellaria lateriflora L. Standards of Analysis, Quality Control and Therapeutics. Scotts Valley, CA: American Herbal Pharmacopoeia; 2009.

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